Bilateral Granulomatous Panuveitis in A Patient with COVID-19.

PURPOSE: To present a case of panuveitis with granulomatous intraocular inflammation and vasculitis related to coronavirus disease 2019 (COVID-19). CASE REPORT: A 46-year-old female patient had blurred vision in both eyes during 8 days after COVID-19 symptoms. Anterior segment examination revealed anterior chamber cells in the both eyes, mutton fat keratic precipitates and posterior synechiae in the left eye. Small peripheral iris nodules and mild vitritis were accompanying in both eyes. Fundus examination revealed multiple superficial retinal infiltrate lesions in the peripheral retina with retinal periphlebitis in both eyes. Spectral domain optical coherence tomography showed hyperreflective superficial retinal infiltrates. Fluorescein angiography (FA) and indocyanine green angiography demonstrated hypofluorescent foci due to blockade of retinal infiltrates. Peripheral vascular leakage was detected on FA in both eyes. CONCLUSION: This case showed that COVID-19 infection can cause granulomatous panuveitis. Autoimmune mechanisms related to COVID-19 may lead to ocular inflammation.

Describing the Clinical and Laboratory Features and HLA-B Pattern of Adult-Onset Idiopathic Autoimmune Uveitis at a Tertiary Hospital in South India: A Cross-Sectional Study.

INTRODUCTION: There is a scarcity of information available on clinical and laboratory features of adult-onset idiopathic autoimmune uveitis. Therefore, we conducted a single centre descriptive cross-sectional study. Patients and Methods. A chart review of all patients with idiopathic autoimmune uveitis with onset after 18 years of age who were referred to the rheumatology department between January 2017 and December 2018 was performed. Their clinical features, demographic features, and HLA-B genotypes were documented and described. RESULTS: Out of 210 patients referred to rheumatology, 66 were found to have uveitis, and 16 of these had an adult-onset idiopathic autoimmune uveitis. Apart from a slight female preponderance (62.5%), our patients were characterized by a high proportion of panuveitis (4 out of 16, i.e., 25%). There was an increased frequency of occurrence of synechiae (5 out of 16, i.e., 31.3%), retinal vasculitis (4 out of 16, i.e., 25%), optic disc edema (3 out of 16, i.e., 18.8%), and cystoid macular edema (seen in 2 patients, i.e., 12.5%). These features correlated with the anatomical subtypes. Retinal vasculitis and optic disc edema present in three fourth of all panuveitis cases were the most prominent features. The odds of finding HLA-B∗35 in retinal vasculitis were 33 times higher than odds of finding it in idiopathic autoimmune uveitis patients not having retinal vasculitis (OR 33; 95% CI 1.6-698). CONCLUSION: Idiopathic autoimmune uveitis in our patients is characterized by a high frequency of panuveitis and retinal vasculitis, and complications with a probable association between HLA-B∗35 and retinal vasculitis.

Features of ectopic lymphoid-like structures in human uveitis.

Persistent non-infectious uveitis has a significant morbidity, but the extent to which this is accompanied by inflammation driven remodelling of the tissue is unclear. To address this question, we studied a series of samples selected from two ocular tissue repositories and identified 15 samples with focal infiltration. Eleven of fifteen contained lymphocytes, both B cells (CD20 positive) and T cells (CD3 positive). In 20% of the samples there was evidence of ectopic lymphoid like structures with focal aggregations of B cells and T cells, segregated into anatomically different adjacent zones. To investigate inflammation in the tissue, an analysis of 520 immune relevant transcripts was carried out and 24 genes were differentially upregulated, compared with control tissue. Two of these (CD14 and fibronectin) were increased in ocular inflammation compared to control immune tissue (tonsil). We demonstrate that in a significant minority of patients, chronic persistent uveitis leads to dysregulation of ocular immune surveillance, characterized by the development of areas of local ectopic lymphoid like structures, which may be a target for therapeutic intervention directed at antibody producing cells.

Supposed endogenous endophthalmitis caused by Serratia marcescens in a cat.

An 8-year-old male neutered domestic shorthair cat was presented for evaluation of acute respiratory distress. Respiratory auscultation revealed a diffuse and symmetric increase in bronchovesicular sounds. Thoracic radiographs showed a diffuse unstructured interstitial pulmonary pattern with multifocal alveolar foci. Despite an aggressive treatment with supportive care, including oxygenotherapy and systemic antibiotics, progressive respiratory distress increased. Three days after the presentation, acute anterior uveitis was noticed on left eye. Ophthalmic examination and ocular ultrasonography revealed unilateral panuveitis with ocular hypertension. The right eye examination was unremarkable. Cytological examination of aqueous humor revealed a suppurative inflammation. Serratia marcescens was identified from aqueous humor culture. Primary pulmonary infection was suspected but was not confirmed as owners declined bronchoalveolar lavage. Active uveitis resolved and cat's pulmonary status improved after appropriate systemic antibacterial therapy. Vision loss was permanent due to secondary mature cataract. To the best of authors' knowledge, this is the first report of endogenous bacterial endophthalmitis secondary to S. marcescens infection in a cat.

CLINICAL PATHOLOGIC CORRELATION OF SARCOIDOSIS-ASSOCIATED MULTIFOCAL CHORIORETINITIS IN AN ELDERLY PATIENT.

BACKGROUND/PURPOSE: To describe a case of histopathologic clinical correlation of sarcoidosis-related multifocal chorioretinitis in an elderly individual. METHODS: This is a single case report and review of the pertinent literature. A 72-year-old white woman with a history of asthma was referred with bilateral asymmetric low-grade chronic panuveitis with advancing peripheral punched-out chorioretinal lesions despite systemic corticosteroid treatment. RESULTS: Coalescent chorioretinal punched-out lesions on fundus examination in the more severely affected right eye did not respond to corticosteroid treatment, and the refractory nature resulted in a suspicion of intraocular lymphoma despite a previous inconclusive diagnostic vitrectomy result. A transvitreal chorioretinal biopsy in the vitrectomized eye demonstrated a chorioretinal noncaseating granuloma centered on the choriocapillaris and invading Bruch membrane and the outer retina. This case illustrates an example of the second peak of incidence in sarcoidosis that can occur in ages >50 in Caucasians and Japanese patients, as well as a tendency to develop chronic disease in Caucasians, and to have extrapulmonary sarcoidosis in the elderly. CONCLUSION: This case emphasizes the differences in presentation of ocular sarcoid in older Caucasian women as well as the histopathologic findings in multifocal peripheral chorioretinitis associated with sarcoidosis.

Seasonal Hyperacute Panuveitis in Nepal: A Review over 40 Years of Surveillance.

Purpose: This review aims to provide a detailed update in Seasonal hypercute panuveitis (SHAPU) which is a blinding disease of unknown etiology reported only from Nepal, occurring every odd year since 1975 predominantly in children. Methods: Data sources were literature reviewed using PubMed, Medline, and ISI Databases (since 1975 to late 2017). Search items included SHAPU, seasonal endophthalmitis, hypopyon uveitis, caterpillar induced uveitis alone or in combination with white moth, panuveitis, and review. Results: Epidemics of SHAPU occur between August to December usually in odd years. Two thirds of the children present with unilateral blind eye which eventually becomes soft with shallowing of anterior chamber called as Malignant Hypotension. Hypopyon, fibrinous exudates in anterior chamber, difficult to dilate pupil and inability to visualize the retina because of massive exudation into vitreous producing a "White pupil in a Red eye" with little or no pain is its characteristic features. Contact with moths has been suspected. Because of presence of microbial agents in few cases, an infectious etiology has not been ruled out. Conclusions: Although SHAPU has been reported only from Nepal, lack of its report from ecologically similar terrain along Hindukush Mountains and possible association with moths remain intriguing.

Sarcoid uveitis in a patient with multiple neurological lesions: a case report and review of the literature.

BACKGROUND: Neurosarcoidosis is a rare complication, and cranial neuropathy is the most frequent manifestation of this disease. However, few cohesive reports have discussed multiple cranial neuropathies in Japanese patients with sarcoidosis. The present report discusses the case of a patient with sarcoid uveitis and multiple neurological findings. We further review relevant literature regarding Japanese patients with multiple cranial nerve palsies published within the past 34 years (from January 1982 to December 2016). CASE PRESENTATION: We report findings associated with the case of a 56-year-old Japanese woman with granulomatous pan-uveitis who was later diagnosed as having sarcoidosis by skin and transbronchial lung biopsies. She presented right-sided Bell's palsy and was treated with orally administered prednisolone. However, while prednisolone was tapered, she developed facial (VII) and vagus (X) nerve palsies, followed by brain parenchyma lesions, which were not associated with any additional neurological symptoms. Furthermore, she exhibited increased intraocular pressure in her right eye, and she underwent trabeculectomy. Our review of the literature revealed that 64 Japanese patients with sarcoidosis experienced multiple cranial nerve palsies between 1982 and 2016. The most commonly affected cranial nerves were the facial (VII) (73.4%) and glossopharyngeal/vagus (IX/X) nerves (48.4%). Palsies of two distinct cranial nerves were found in 40.6% of the patients, followed by palsies of three (23.4%) and four (18.8%) nerves. Almost all patients (98.3%) received systemic steroid therapy, and total or partial remission was achieved in almost all patients (96.5%). CONCLUSIONS: According to the literature, patients with multiple cranial nerve palsies associated with sarcoidosis respond well to orally administered steroid therapy. However, our findings suggest that careful follow-up is necessary for patients with neurosarcoidosis due to potential aggravation of neuropathy.

Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the Treatment of Experimental Uveitis Rabbit.

PURPOSE: To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. METHODS: Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency. Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and histopathological examinations for ocular inflammations and pathology. RESULTS: The control group exhibited panuveitis with significant inflammation in the vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior chamber. The uveitis occurred within 24 h after induction and persisted throughout the study in the control group. All treatments showed some reduction in inflammation in the vitreous, choroid, and retina. The higher dose regimens generally showed more rapid and higher degree of resolution than the lower dose regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex eyes showed minimal response. CONCLUSIONS: All DSP-Visulex regimens suppressed the signs of inflammation and were well tolerated over the course of a 29-day study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP-Visulex regimen may only be considered for anterior and intermediate uveitis.

Observation and Clinical Pattern in Patients with White Dot Syndromes: The Role of Color Photography in Monitoring Ocular Changes in Long-Term Observation.

BACKGROUND The aim of this study was to assess the clinical course and distinctive features of different white dot syndromes (WDS) in patients attending the Ophthalmology Department, Medical University of Warsaw in the years 1995-2015. MATERIAL AND METHODS Sixty-two (62) patients (43 females and 19 males), aged 18 to 77 years, referred with a WDS were included in this prospective study, with observation period ranging from 5 months to 16 years. All patients underwent a complete ophthalmological examination and multimodal imaging studies. RESULTS In this cohort of 62 patients, the following WDS entities were identified: multifocal choroiditis with panuveitis (MFCPU), multifocal choroiditis (MFC), punctate inner choroidopathy (PIC), birdshot, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), subretinal fibrosis and uveitis, multiple evanescent white dot syndrome (MEWDS), serpiginous choroiditis, and single cases of acute annular outer retinopathy (AAOR). CONCLUSIONS The study was performed at a Polish referral center and may to some extent reflect the varied geographical distribution of white dot syndromes, as none of the subjects was found to suffer from acute zonal occult outer retinopathy (AZOOR), acute macular neuroretinopathy (AMN), or diffuse unilateral subacute neuroretinitis (DUSN). Long-term follow-up is warranted by the evolution of lesions in the eye fundus, while management depends on correct diagnosis of WDS. When the posterior pole is involved in some cases of the WDS an immunosuppressive treatment, the use of the PDT or anti-VEGF injections were necessary.

Choroidal neovascularisation on optical coherence tomography angiography in punctate inner choroidopathy and multifocal choroiditis.

PURPOSE: To describe the findings seen on optical coherence tomography angiography (OCTA) in patients with punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) complicated by choroidal neovascular membranes. METHODS: This was an Institutional Review Board-approved prospective, descriptive case series. 12 patients with PIC and MCP complicated by choroidal neovascularisation (CNV) were included. Each patient underwent slit-lamp examination by a uveitis specialist followed by conventional spectral domain OCT imaging of the macula. OCTA images of the macula were then obtained. RESULTS: 12 patients were enrolled in the study, out of which 9 patients were followed longitudinally. CNV was identified in 11 of the 12 patients. In all patients where fluorescein angiography (FA) was inconclusive for presence of CNV, OCTA identified CNV. Various lesions on OCT suggestive of activity correlated with changes in the vascular structure of OCTA to confirm suspicion of clinical activity. CONCLUSION: In patients with PIC and MCP complicated by CNV, OCTA successfully identified underlying CNV. Given the difficulty of differentiating inflammatory lesions from early CNV on OCT and FA, OCTA may provide a valuable method of monitoring patients with posterior uveitis highly correlated with development of CNV.

A Rare Case of Pembrolizumab-Induced Uveitis in a Patient with Metastatic Melanoma.

Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is a humanized monoclonal antibody used in the treatment of metastatic or unresectable melanoma and advanced non-small cell lung cancer (NSCLC). We hereby report a case of pembrolizumab-induced uveitis to increase practitioner awareness. A 78-year-old woman presented with onset of panuveitis after initiation of pembrolizumab therapy for metastatic melanoma. The patient received three cycles of therapy every 21 days, during which her symptoms progressively worsened. She was treated with topical and systemic corticosteroids, and further pembrolizumab was discontinued despite a good response to therapy. Pembrolizumab has been associated with rapid onset of ocular inflammation and uveitis. PD-1 inhibitors mediate a T-cell response against cancer cells; however, autoimmune complications have been reported. Incidence of pembrolizumab-induced uveitis is reported to be < 1%. To date, three cases have been reported since its Food and Drug Administration approval in September 2014. Uveitis, if left untreated, may lead to permanent vision loss and ocular damage. Cases of immune-mediated uveitis have been reported with cancer immunotherapies. Oncologists and ophthalmologists should be aware of this complication. With the increasing targeted pharmaceuticals in oncology, effective management of adverse events is necessary to ensure patient safety and optimal outcomes.

[Vogt-Koyanagi-Harada syndrome].

The Vogt-Koyanagi-Harada syndrome is a disease with dermatological, neurologic and auditory findings, associated with a bilateral granulomatous panuveitis. We present the case of a 42-year-old woman who started with ophthalmic manifestations, and in a late follow-up she developed the characteristic dermatological findings.

Diagnostic efficacy of cell block method for vitreoretinal lymphoma.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a life- and sight-threatening disorder. The aim of this study was to analyze the usefulness of the cell block method for diagnosis of VRL. METHODS: Sixteen eyes in 12 patients with VRL, and 4 eyes in 4 patients with idiopathic uveitis presenting with vitreous opacity were enrolled in this study. Both undiluted vitreous and diluted fluids were isolated during micro-incision vitrectomy. Cell block specimens were prepared in 19 eyes from diluted fluid containing shredding vitreous. These specimens were then submitted for HE staining as well as immunocytological analyses with antibodies against the B-cell marker CD20, the T-cell marker CD3, and cell proliferation marker Ki67. Conventional smear cytology was applied in 14 eyes with VRL using undiluted vitreous samples. The diagnosis of VRL was made based on the results of cytology, concentrations of interleukin (IL)-10 and IL-6 in undiluted vitreous, and immunoglobulin heavy chain gene rearrangement analysis. RESULTS: Atypical lymphoid cells were identified in 14 out of 15 cell block specimens of VRL (positive rate: 93.3 %), but in 5 out of 14 eyes in conventional smear cytology (positive rate: 35.7 %). Atypical lymphoid cells showed immunoreactivity for CD20 and Ki67. Seven cell block specimens were smear cytology-negative and cell block-positive. The cell block method showed no atypical lymphoid cells in any patient with idiopathic uveitis. CONCLUSIONS: Cell block specimens using diluted vitreous fluid demonstrated a high diagnostic sensitivity and a low pseudo-positive rate for the cytological diagnosis of VRL. The cell block method contributed to clear differentiation between VRL and idiopathic uveitis with vitreous opacity.

Multifocal choroiditis and panuveitis presenting with progressive equatorial linear streaks: evolution of Schlaegel lines documented with multimodal imaging.

PURPOSE: To describe the progressive, peripheral linear streaks of the equatorial retina, known as Schlaegel lines, in multifocal choroiditis and panuveitis (MCP). METHODS: A case report of a 13-year-old girl with MCP showed progression of retinal linear streaks. Extensive systemic and ophthalmologic investigations were performed. RESULTS: Linear streaks in MCP showed progression before the institution of immunomodulatory treatment. Infrared imaging showed hyperreflectivity of the lesions with surrounding hyporeflectivity. Optical coherence tomography showed elevated and irregular hyperreflectivity of the retinal pigment epithelium and choroidal hyperreflectivity. These findings, including the clinical progression before immunomodulatory therapy and negative systemic evaluation for infectious entities, are consistent with MCP. CONCLUSION: Patients with linear streaks in the setting of atypical MCP can progress and should be treated with adequate systemic corticosteroids and immunomodulatory agents. This case is unique in that it shows the evolution of Schlaegel lines using a multimodal imaging approach. Multimodal imaging can provide ancillary evidence of disease activity.

Panuveitis caused by Borrelia burgdorferi sensu lato infection.

A 13-year-old boy who presented with a red left eye, painful eye movement, blurred vision, photophobia and increased lacrimation, was diagnosed with 1-sided panuveitis with optic disk edema. Diagnostic work-up revealed borrelial antibodies in serum. Diagnosis of Lyme borreliosis was substantiated by demonstration of lymphocytic pleocytosis, intrathecal borrelial antibody synthesis, improvement after treatment with ceftriaxone and exclusion of other causes.