Ocular Sarcoidosis Research Articles

Clinical Usefulness of the Revised International Workshop for Ocular Sarcoidosis Criteria in Korean Patients

Purpose: To compare differences between the original criteria for diagnosis of ocular sarcoidosis (OS) (first International Workshop for OS [IWOS] 2009) and the revised criteria (sixth IWOS 2017), and their clinical usefulness when assessing OS in Korean patients. Methods: We analyzed patients with suspected OS who visited our tertiary referral ophthalmological and pulmonary clinic from 2007 to 2018. We diagnosed patients using both sets of criteria. Blood test and biopsy data (collected by physicians) and slit-lamp, fundus, and fluorescein angiography data (collected by ophthalmologists) were reviewed. Results: Thirty-four patients were diagnosed using both criteria. Of 32 patients who underwent biopsies, 31 had OS (96.87%). Using either set of criteria, 31 patients were diagnosed with definite OS and two with presumed OS. One patient diagnosed with possible OS using the previous criteria was diagnosed with presumed OS using the revised criteria. The new criteria add the lysozyme level, the CD4/CD8 ratio, and positron emission tomography imaging data to the old criteria and add the descriptors “presumed OS” and “probable OS”. There is no need to use the revised criteria in Korea; the biopsy and imaging data are adequately diagnostic. Conclusions: IWOS revised the OS diagnostic criteria by adding new parameters. However, this was unnecessary for Korea, where the biopsy and imaging data are adequately diagnostic.

Identification of microbial agents in tissue specimens of ocular and periocular sarcoidosis using a metagenomics approach.

Background: Metagenomic sequencing has the potential to identify a wide range of pathogens in human tissue samples. Sarcoidosis is a complex disorder whose etiology remains unknown and for which a variety of infectious causes have been hypothesized. We sought to conduct metagenomic sequencing on cases of ocular and periocular sarcoidosis, none of them with previously identified infectious causes. Methods: Archival tissue specimens of 16 subjects with biopsies of ocular and periocular tissues that were positive for non-caseating granulomas were used as cases. Four archival tissue specimens that did not demonstrate non-caseating granulomas were also included as controls. Genomic DNA was extracted from tissue sections. DNA libraries were generated from the extracted genomic DNA and the libraries underwent next-generation sequencing. Results: We generated between 4.8 and 20.7 million reads for each of the 16 cases plus four control samples. For eight of the cases, we identified microbial pathogens that were present well above the background, with one potential pathogen identified for seven of the cases and two possible pathogens for one of the cases. Five of the eight cases were associated with bacteria ( Campylobacter concisus, Neisseria elongata, Streptococcus salivarius, Pseudopropionibacterium propionicum, and Paracoccus yeei), two cases with fungi ( Exophiala oligosperma, Lomentospora prolificans and Aspergillus versicolor) and one case with a virus (Mupapillomavirus 1). Interestingly, four of the five bacterial species are also part of the human oral microbiome. Conclusions: Using a metagenomic sequencing we identified possible infectious causes in half of the ocular and periocular sarcoidosis cases analyzed. Our findings support the proposition that sarcoidosis could be an etiologically heterogenous disease. Because these are previously banked samples, direct follow-up in the respective patients is impossible, but these results suggest that sequencing may be a valuable tool in better understanding the etiopathogenesis of sarcoidosis and in diagnosing and treating this disease.

Associations between occupational and environmental exposures and organ involvement in sarcoidosis: a retrospective case-case analysis

BackgroundSarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.ObjectiveTo investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosisMethodsWe retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.ResultsWe included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79).ConclusionsOur study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

A Case of Unilateral Choroidal Granuloma as a Sole Presentation of Sarcoidosis

<strong>Introduction:</strong> Sarcoidosis is an inflammatory disease that affects multiple organs in the body, but mostly the lungs and lymph glands. It is one of the leading causes of inflammatory eye disease. The most common ocular manifestations are uveitis and conjunctival involvement. However, it can involve any part of the eye and its adnexal tissues and cause episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Rarely, it can present as bilateral choroidal granuloma. However, choroidal granuloma without other signs of intraocular inflammation and/or systemic involvement is an extremely rare manifestation. <strong>Case Description:</strong> A 38-year-old African American woman came to the ophthalmology service with the primary complaint of decreased visual acuity in her right eye and right eye pain. Upon examination, a serous macular detachment secondary to central serous retinopathy and a solitary choroidal granuloma were observed. On physical examination, she had eyelid enlargement and facial papules. Laboratory findings showed elevated ACE, while ANA, ANCA, Lyme, Syphilis, anti-dsDNA, QuantiFERON, RF, IL-2 R and lysozyme were all negative. A CT of the chest showed only mildly increased mediastinal lymph nodes in the right paratracheal region. Ophthalmology, rheumatology, and pulmonary teams were involved in further management. Treatment was started with daily oral prednisone and consequent addition of methotrexate which eventually resulted in reduced size of granuloma, resolution of the eye pain and improvement in vision. <strong>Discussion:</strong> There is no single way to diagnose sarcoidosis. Primary occurrence is, most often, between 20 and 40 years of age, with women being diagnosed more frequently than men. The disease is 10 to 17 times more common in African Americans than in Caucasians. The main diagnostic tools include Chest X-rays and high-resolution CT scan to look for pulmonary infiltrates or lymphadenopathy. Some patients with sarcoidosis may have elevated serum calcium levels, angiotensin converting enzyme (ACE) and/or lysozyme. The gold standard for the diagnosis is a tissue biopsy. However, suspected lesions may not be easily accessible, as in this case where only the eye was affected. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues. A solitary choroidal granuloma is one of the manifestations recognized in sarcoidosis, though the much more common manifestation is bilateral uveitis (reported in 30–70% of cases) and conjunctival nodules (found in 40% of cases). Ophthalmic manifestations can be isolated but most patients have evidence of systemic involvement at the time of the initial examination and have bilateral ocular presentation, unlike this patient who had solitary, unilateral choroidal granuloma without other signs of intraocular inflammation and systemic involvement. <strong>Conclusion:</strong> There are several cases of sarcoidosis reporting choroidal granuloma with either other ocular involvements and/or associated hilar lymphadenopathy and other systemic manifestations. This patient is a rare case where the sole presentation of sarcoidosis is a unilateral solitary granuloma. Biopsy was not feasible due to location of the lesion. This case shows the importance of a multi-disciplinary approach in rare cases where the gold standard for diagnosis is not possible.

Ocular sarcoidosis: a case report

Introduction: Sarcoidosis is a chronic granulomatous disorder which affects almost all parts of the body. It is usually idiopathic. Ocular involvement is noted in 25%–60% of patients with systemic sarcoidosis. It is very essential to rule out ocular tuberculosis as both can have similar presentations. Case report: A 26 year old patient presented with blurring of vision in left eye for nine months at Mongar regional referral hospital. Previously he was treated with topical steroids and cycloplegics for anterior uveitis. There were no systemic symptoms like dry cough, fever, chest pain and loss of weight. He had anterior chamber inflammation with iris nodule, vitritis and disc edema in left eye.The right eye had minimal anterior chamber reaction with only subtle iris nodule. Posterior segment examination was normal in right eye. He underwent blood investigations, chest X ray and contrast enhanced computed tomography of chest(CECT). The blood reports were normal. The chest X ray showed radiopaque lesions at both hilar region and multiple tiny radiopaque lesions in both lung fields.CECT chest showed significant paratracheal lymph nodes.Lymph node biopsy was not attempted due to extreme location. Based on clinical presentations and investigation findings a diagnosis of Presumed ocular sarcoidosis was made by using the criteria based on Revised International Workshop on Ocular Sarcoidosis.The patient was treated effectively with oral steroids for six months. Currently he is on low maintenance dose of oral steroids. Conclusions: Ocular sarcoidosis is a potentially blinding condition if not treated on time. There should be high suspicion of ocular sarcoidosis if patient presents with bilateral granulomatous anterior uveitis with hilar lymphadenopathy.However it is crucial to exclude ocular tuberculosis as both are mimickers of chronic granulomatous uveitis.

Granulomatous and sarcoid-like immune related adverse events (irAEs) in melanoma patients following CTLA4 blockade adjuvant therapy: An analysis of 1670 high-risk patients.

9582 Background: Granulomatous and sarcoid-like lesions (GSL) affecting the skin, lungs, thoracic lymph nodes, eyes and other organs following treatment with immune checkpoint inhibitors (ICIs) have been described in sporadic reports in the literature but the true incidence is unknown. Methods: We sought to estimate the incidence of GSL in the context of prospectively conducted ECOG-ACRIN E1609 phase III adjuvant trial in high-risk resected melanoma (N=1670 patients) testing ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose interferon-α (HDI). Descriptive statistics were used to calculate the incidence. Results: Among 1670 total patients treated with ICIs or with HDI in E1609, 1034 were treated with ipilimumab and 636 with HDI. Six GSL cases were reported among 1670 total patients treated with ipilimumab or with HDI as summarized in the table along with the corresponding CTCAE grades. More cases were observed with ipi10, followed by ipi3 and HDI, respectively. Organs involved included skin and subcutaneous tissue (granuloma annulare, granulomatous dermatitis), eye (ocular sarcoidosis), lymph nodes (noncaseating granulomatous lymphadenitis), lung and mediastinal lymph nodes (sarcoidosis, granulomatous inflammation). Conclusions: The incidence of granulomatous and sarcoid-like lesions (GSL) with adjuvant ipilimumab therapy in high-risk melanoma is rare. Reported cases ranged in grade from 1-3 and appeared manageable. Since most cases are asymptomatic, it is possible that GSLs are under-recognized and therefore, under-reported. A larger analysis including patients treated with anti-PD1 antibodies is currently underway. Clinical trial information: NCT01274338. [Table: see text]

POS0740 EPIDEMIOLOGY AND CLINICAL FEATURES OF OCULAR SARCOIDOSIS. STUDY OF 65 PATIENTS OF A SERIES OF 384 PATIENTS FROM A SINGLE UNIVERSITY HOSPITAL

Background:Ocular involvement in sarcoidosis can be present in up to 80% of patients. If not treated, it can lead to significant visually complications (1-5).Objectives:Our aim was to assess the main a) epidemiology and b) clinical features of ocular sarcoidosis in a wide and unselected series from a single university hospital.Methods:Study of a large cohort (n=384) of all consecutive patients diagnosed with sarcoidosis from January 1, 1999 to December 31, 2019. Finally, 344 patients were included according to the ATS/ERS/WASOG criteria (Eur Respir J. 1999;14:735-7).Results:65 (33 men/32 women) of 344 (18.9%) patients had ocular involvement. Mean age at diagnosis was 45.6±15.9 years. The most frequent extraocular clinical clusters were respiratory (80%), osteoarticular (30.8%) and cutaneous (29.2%) (figure 1). Ocular manifestations and complications are shown in table 1. Uveitis (83.1%), orbital lesions (7.7%) and retinal vasculitis (6.2%) were the most common ocular lesions. Median Best Corrected Visual Acuity (BCVA) at diagnosis and after one year of follow-up was 0.6 [0.3-0.8] and 0.9 [0.30-1], respectively. Retinal vasculitis was associated to the worst BCVA outcome, and panuveitis to more frequent and severe complications.Conclusion:Ocular manifestations, especially uveitis, are frequent in sarcoidosis. A more aggressive and early treatment may be indicated in panuveitis and retinal vasculitis.

Characteristics of Serum Ratios of 1,25-Dihydroxyvitamin D to 25-Hydroxyvitamin D for Assessment of Bone Metabolism

Vitamin D is obtained in the body by food intake or by production from 7-dehydrocholesterol by exposure of the skin to ultraviolet B radiation. It is first metabolized in the liver to 25-hydroxyvitamin D (25D), which is a major circulating metabolite. In the kidney, 25D is subsequently metabolized to the hormonally active form, 1,25-dihydroxyvitamin D (1,25D), via 1α-hydroxylase encoded by the CYP27B1 gene. 1,25D has a cellular effect through the vitamin D receptor, which leads to calcium absorption in the gut, bone metabolism, and parathyroid function. A recent study showed that a low vitamin D status is common worldwide and is associated with various diseases including kidney, heart, and liver failure, secondary hyperparathyroidism, osteomalacia, inflammatory bowel disease, granuloma-forming disorders (sarcoidosis and tuberculosis), and cancer. Vitamin D deficiency also increases the risks of falls, fractures, bone loss, sarcopenia, leading to worse outcomes of illness severity, morbidity, and mortality. The 1,25D/25D ratio is considered to be a useful tool for diagnosis of ocular sarcoidosis; however, its clinical utility and relevance to pathophysiology of evaluation of the ratio 1,25D/25D which indicates vitamin D activation have remained unknown. To clarify the clinical usefulness of markers for vitamin D activation, 87 patients in whom serum 25D and 1,25D level was measured were retrospectively reviewed in the present study. Data for 79 patients (33 males and 46 females) were analyzed after exclusion of 8 patients taking vitamin D. The median serum 1,25D/25D ratio was significantly lower in males than in females: 4.1 (IQR: 2.3–5.8) x 10−3 versus 6.8 (3.0–9.8) x 10−3. However, individual levels of 25D and 1,25D were not different in males and females. The major categories of main disorders were endocrine (30.6 %), inflammatory (18.5 %), and bone-related (16.7 %) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between 1,25D/25D ratio and serum levels of inorganic phosphate (R=-0.34), intact parathyroid hormone (R=0.64) and alkaline phosphatase (R=0.46) in all patients. Of interest, the 1,25D/25D ratio had gender-specific characteristics: the ratio had a significant correlation with age in males (R=0.49), while it had a significant correlation with body mass index (BMI) in females (R=0.34). Collectively, the results revealed that the ratio of serum 1,25D/25D as a marker for activation of vitamin D had relevance to clinical parameters, especially bone turnover, with gender-specific features. It is suggested that the existence of a gender-specific difference of aging males and obese females regarding the activation of vitamin D that is functionally linked to bone metabolism.

Pathogenesis of Non-Infectious Uveitis Elucidated by Recent Genetic Findings.

Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet’s disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet’s disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by IL23R, is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient’s genetic make-up is expected.

Outcomes of Repository Corticotropin Gel for Ocular Sarcoidosis

ABSTRACT Purpose: To evaluate the utility and side effect profile of subcutaneous repository corticotropin gel (RCI) in ocular sarcoidosis. Methods: Retrospective chart review. Results: Among six identified patients on RCI therapy, 4 had uveitis, one had optic neuritis and one had uveitis and optic neuritis secondary to sarcoidosis. The average follow-up was 43.5 months. RCI therapy was continuous in 4 patients (average 7.7 months) and intermittent in 2 patients (24 and 12 months). Five of the 6 patients continued with local and/or systemic corticosteroids for ocular inflammation control while on RCI therapy. Two-thirds of patients experienced adverse effects including hyperpigmentation, alopecia, and severe hypertension. RCI therapy was discontinued in 5 of the 6 patients due to continued inflammation and side/adverse effects (4 patients) and loss of follow-up (1 patient). Conclusion: In this small cohort, the majority of patients failed to achieve adequate steroid-sparing ocular inflammation control and experienced side effects while on RCI therapy. Additional studies are needed to elucidate the role of RCI in ocular inflammation.

Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis.

Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25–50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren’s syndrome, lupus pernio, Heerfordt’s syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.

The Comparative Value of Serum Angiotensin Converting Enzyme (ACE) and Lysozyme and the Use of Polyclonal Antibody Activation in the Work-up of Ocular Sarcoidosis.

Background: The diagnosis of ocular sarcoidosis (OS) is difficult to establish in the absence of manifest systemic involvement. To help clinicians reach a diagnosis, we convened a group of experts in 2006 (International Workshop on Ocular Sarcoidosis (IWOS)) to set-up clinical criteria for the diagnosis of ocular sarcoidosis. In addition, laboratory investigational tests represent a much-needed adjunct to ascertain the diagnosis. However, many of these tests have low sensitivity and specificity. Purpose: The aim of our study was to evaluate the usefulness of serum ACE, serum lysozyme and polyclonal antibody activation in the diagnosis of ocular sarcoidosis and compare the frequency of increased serum levels of lysozyme and ACE in proven ocular sarcoidosis or in suspected ocular sarcoidosis. Methods: Serum ACE and lysozyme were assessed in these two groups and their means compared to a group of non-granulomatous (i.e., non-sarcoidosis) uveitis patients. The proportion of elevated serum ACE versus lysozyme was compared in the sarcoidosis patients. Polyclonal antibody activation was measured by establishing exposition of patients to four human commensal herpesviruses (EBV, CMV, HSV and VZV) using ELISA or immunofluorescence and in parallel by performing quantitative complement fixation (CF) serologies. The ratio of elevated CF to positive ELISA/immunofluorescence serologies was calculated. The mean of ratios (polyclonal antibody activation) was compared between ocular sarcoidosis and control groups. Results: Thirty-seven patients (F24/M13) were included in our study including 17 patients with IWOS Level 1 and 2 criteria qualifying for Group 1 (proven sarcoidosis) and 20 ocular sarcoidosis suspect patients. Mean age was 54.52 ± 23.74. Mean serum levels of ACE was 49.17± 29 IU/L in the ocular sarcoidosis group versus 27.4 ± 15.34 IU/L (p ≤ 0.00018, student’s t test) in the control group. Mean serum lysozyme levels was 39.92 ± 55.5 mg/L in the ocular sarcoidosis group versus 10.5 ± 5.8 mg/L (p ≤ 0.0013) in the control group (n = 30). Both tests were elevated in 8/37 (21.6%) patients, elevated ACE and normal lysozyme was noted in 2/37 (5.4%) patients, whereas the proportion of normal ACE/elevated lysozyme was much higher, 23/37 (62.2%). In 4/37 (10.8%) patients, both tests were normal. The mean score of polyclonal activation (N of elevated CF serologies divided by number of viruses to which a patient was exposed) was 0.6 ± 0.33 in the ocular sarcoidosis group versus 0.15 ± 0.2 for the control group (n = 42) (p ≤ 0.00001). Sensitivity and specificity of ACE and lysozyme were, respectively, 27%/96.6% and 83.7%/90%. Sensitivity and specificity of polyclonal antibody activation amounted to 70%/90.4% Conclusion: Lysozyme was found to be much more useful than ACE as a laboratory test to support the diagnosis of ocular sarcoidosis. As shown in a previous study, polyclonal antibody activation appears to be another useful laboratory test supportive of the diagnosis of ocular sarcoidosis.

Systemic Associations of Sarcoid Uveitis: Correlation With Uveitis Phenotype and Ethnicity

To examine systemic associations of sarcoid uveitis and association with uveitis clinical phenotype and ethnicity. Retrospective cross-sectional study. A total of 362 subjects with definite or presumed sarcoid uveitis from Moorfields Eye Hospital, Royal Victorian Eye and Ear, and Auckland District Health Board. Data were collected from the review of clinical notes, imaging, and investigations. Sarcoidosis was diagnosed in accordance with the International Workshop on Ocular Sarcoidosis guidelines. Diagnosis of associated systemic disease secondary to sarcoidosis. A total of 362 subjects with sarcoid uveitis were identified. Median age was 46 years, and 226 (62.4%) were female. Granulomatous anterior uveitis (47.8%), intermediate uveitis with snowballs (46.4%), and multifocal choroiditis (43.1%) were the most frequent clinical presentations, and disease was bilateral in 313 (86.5%). Periphlebitis was observed in 21.0%, and solitary optic nerve or choroidal granuloma in 11.3%. Lung parenchymal disease was diagnosed in 200 subjects (55.2%), cutaneous sarcoid in 98 (27.1%), sarcoid arthritis in 57 (15.7%), liver involvement in 21 (5.8%), neurosarcoid in 49 (13.5%), and cardiac sarcoid in 16 subjects (4.4%). Subjects with cardiac sarcoid were less likely to have granulomatous anterior uveitis (P=.017). Caucasian subjects were older at presentation (48 vs 41 years; P=.009), had less granulomatous anterior uveitis (26.4% vs 51.7%; P < .001), and were less likely to present with cutaneous involvement (23.1% vs 35.4%; P=.040). Ophthalmologists need to be aware of the systemic associations of sarcoid uveitis, in particular potentially life-threatening complications such as cardiac sarcoidosis. Differences observed in uveitis phenotype and between ethnicities require further investigation.

A Rare Presentation of Solitary Ocular Sarcoidosis

Ocular sarcoidosis leads to inflammation of the eye, manifesting as uveitis, scleritis and conjunctivitis with granuloma formation. It can involve any part of the eye and its adnexal tissues, and may result in complications like glaucoma and cataract. Ophthalmic manifestations of sarcoidosis can be isolated, or it may be associated with other organs of the body. The clinical presentation in ocular sarcoidosis is quite varied. Multi-disciplinary modality of treatment is required for both ocular and systemic manifestations of the disease. We report a rare presentation of solitary ocular sarcoidosis in a 42-year-old woman, who presented with complaints of painless left inner canthus swelling and blurry vision for 1 month.

Evaluation of Lamina Cribrosa by Using Enhanced Depth Imaging Optical Coherence Tomography in Ocular Sarcoidosis during Quiescent Phase.

Enhanced depth imaging optical coherence tomography is a useful method to allow for the evaluation of deep ocular structures, such as choroid and lamina cribrosa (LC), which are affected by ocular diseases. We hypothesized that choroidal and optic nerve inflammation in patients with ocular sarcoidosis (OS) might affect the LC structure. This study aimed to evaluate changes in the LC and anterior LC depth (ALCD) in patients with OS. Forty-eight eyes of 26 patients with OS who received the treatment of panuveitis and were in the quiescent phase for at least 6 months were included in the study. Thirty healthy subjects' randomly selected eyes were selected as a control group. Eyes with OS were divided into two subgroups according to the presence (OS eyes with glaucoma [OSWG], n = 23) or absence of glaucoma (OS eyes without glaucoma [OSWOG], n = 25). The LC thickness, ALCD, and peripapillary choroidal thickness were measured using enhanced depth imaging optical coherence tomography in eyes with OS and in controls. The mean LC thickness was found significantly thinner in both OSWG and OSWOG eyes compared with the healthy controls (P < .001 and P = .001, respectively). The mean ALCD was found significantly higher in OSWG eyes (462 ± 65 μm) compared with OSWOG eyes (417 ± 58 μm) and the healthy control eyes (397 ± 59 μm; P = .03 and P = .001, respectively). The average peripapillary choroidal thickness was found to be significantly thinner in OSWG eyes compared with the control eyes (P = .05). The present study revealed that OS is associated with a thinned LC independent of the presence of glaucoma. The degenerative changes in the LC, which is the transition point of the retinal nerve fibers, may cause long-term visual dysfunction in OS. These degenerative changes should be prevented by controlling inflammation with early diagnosis and treatment in patients with OS.

Validation of systemic parameters for the diagnosis of ocular sarcoidosis.

Ocular sarcoidosis is diagnosed based on suggestive intraocular findings and systemic investigations. In this study, we assessed the clinical usefulness of systemic parameters in the diagnosis of ocular sarcoidosis. A retrospective study. This study included 79 cases (19 men, 60 women) with ocular sarcoidosis who visited Hokkaido University Hospital from 2011 to 2015 and were followed up for more than one year. The control group was 91 cases of other uveitis (38 men, 53 women). All cases underwent blood examination for the measurement of angiotensin-converting enzyme (ACE), Krebs von den Lungen-6 (KL-6), soluble interleukin-2 receptor (sIL-2R), and calcium (Ca) levels. Bilateral hilar lymphadenopathy (BHL) was also examined by plain chest X-ray and contrasting chest computed tomography (CT). The sensitivity for sIL-2R (76.4%) was higher than for ACE (37.7%), KL-6 (26.3%), and Ca (11.8%), although all showed high specificity: ACE (97.5%), KL-6 (96.2%), sIL-2R (93.8%), and Ca (95.1%). From these results, the Youden index of sIL-2R (0.70) was higher than that of ACE (0.35), KL-6 (0.26), and Ca (0.07). Imaging tests revealed better detection of BHL by contrasting chest CT (82.7%) than by plain chest X-ray (29.5%). The present findings indicate that the systemic parameters, particularly serum sIL-2R levels and BHL on contrasting chest CT, are useful biomarkers for the diagnosis of ocular sarcoidosis.

Sarcoidosis and Ocular Involvement

Sarcoidosis is an inflammatory systemic disease characterized by non-caseifying granulomas at the histopathological level. Ocular sarcoidosis has many symptoms and signs. Currently, the diagnosis of sarcoidosis remains a problem, especially in extrapulmonary involvement. Local and/or systemic corticosteroids and immunomodulators are used in the treatment depending on the location of the anatomical involvement in the eye and the severity of inflammation. In the future, specific genes will be utilized in the diagnosis of sarcoidosis and will be able to reveal its infectious etiology in microbiological developments. And these developments will be able to change the treatment approaches of sarcoidosis.

Поражение орбиты (псевдотумор и дакриоаденит) как манифестация полиорганного саркоидоза

Ocular manifestations of systemic sarcoidosis may emerge at any disease stage. Ocular sarcoidosis is typically characterized by uveitic presentations that predominantly involve the choroid of anterior eye segment. However, orbital pseudotumor, dacryoadenitis, and other rare presentations (optic neuritis, dacryocystitis etc.) also occur in sarcoidosis. Threatened vision loss and poor quality of life are the reasons to prescribe systemic steroids in generalized sarcoidosis. Chest CT is required to identify respiratory diseases when sarcoidosis manifests as uveitis or granulomatous orbital inflammation. Multidisciplinary diagnostic and treatment approach to suspected sarcoidosis provides timely verified diagnosis and management strategy. This paper addresses case report of systemic sarcoidosis in a 34-year-old man. The initial manifestation was vision loss and left orbital pseudotumor. The enlarged subclavian lymph node and its biopsy were suspicious of granulomatous inflammation. Chest CT identified disseminated pulmonary lesions and intrathoracic lymphadenopathy that are typical of sarcoidosis. The results of multidisciplinary examinations verified systemic sarcoidosis. Systemic steroids resulted in clinical and radiological improvement and medicinal regression of the disease. Keywords: sarcoidosis, orbital pseudotumor, dacryoadenitis, adenopathy, computed tomography, multidisciplinary approach. For citation: Burylova E.A., Mamaeva L.A., Berdnikova A.S., Fedorova O.K. Orbital lesion (pseudotumor and dacryoadenitis) is a manifestation of systemic sarcoidosis. Russian Journal of Clinical Ophthalmology. 2021;21(1):40–44. DOI: 10.32364/2311-7729-2021-21-1-40-44.

Microangiopathy in Ocular Sarcoidosis Using Fluorescein Gonio and Fundus Angiography from Diagnostic and Therapeutic Aspects.

In this retrospective study, we investigated vascular abnormalities in sarcoidosis using fluorescein gonioangiography (FGA) to detect angle neovascularization (ANV), fundus fluorescein angiography (FFA), and pathological specimens from the aspects of microangiopathy. In 57 sarcoidosis patients, clinical data was reviewed by dividing the cases into three groups (Group I: histologically diagnosed; Group II: positive bilateral hilar lymphadenopathy (BHL); Group III: negative BHL). The FFA, FGA, and pathological examination data in the autopsy eyes and trabeculectomy specimens were investigated. FGA and FFA detected ANV (91%) and nodule-associated abnormalities (87%), respectively. No intraocular pressure (IOP) elevation was observed after continuous topical betamethasone, except in the steroid responder group. Maximum IOP had significant correlation with nodules in the angle (p = 0.02696) and visual field defect (p = 0.0151). Granulomas adjacent to blood vessels, including the Schlemm’s canal, and thickening of the retinal blood vessel wall caused occlusion of those vessels. Photocoagulation was required for retinal tears (14%) and the retinal blood vessel occlusion (7%). Suppression of IOP elevation via continuous topical betamethasone may be important to avoid irreversible outflow-route changes and optic-nerve damage, and the concept of microangiopathy in ocular sarcoidosis may be important for understanding the proper treatment of serious complications.

A study of ocular sarcoidosis using international workshop for ocular sarcoidosis criteria in a south Indian population

Purpose: To study the clinical profile of patients with ocular sarcoidosis using the new International Workshop for Ocular Sarcoidosis (IWOS) guidelines, in a tertiary care hospital in South India. Materials and Methods: A retrospective observational study where the records of patients diagnosed to have sarcoidosis were analyzed and regraded according to the new guidelines by the International Workshop for Ocular Sarcoidosis. Results: Among the 36 sarcoidosis patient records evaluated in the study period, respiratory involvement was found in 80.6% whereas ocular involvement in 38.9% cases. Uveitis was the most common ocular manifestation seen in 59.1% of those who underwent ocular evaluation. Applying the IWOS guidelines in our patients with uveitis, we found, two had definite ocular sarcoidosis; seven had presumed ocular sarcoidosis; four had probable ocular sarcoidosis and none with possible ocular sarcoidosis. Conclusion: Sarcoidosis is not uncommon in India. Ocular features are common and need to be screened in all patients diagnosed with systemic sarcoidosis. An ophthalmologist can use IWOS criteria in cases of uveitis to clinically diagnose and refer cases for systemic evaluation of sarcoidosis.