Clinical Utility of 18F-FDG PET/CT in the Work-up of Children with Uveitis.

PURPOSE: To evaluate 18F-fluorodeoxyglucose Positron Emission Tomography/ultra low dose Computed Tomography (18F-FDG PET/ ULD CT) in the work-up of pediatric uveitis. METHODS: Retrospective study of 12 children followed for uveitis who underwent whole body 18F-FDG PET/ULD CT between 2011 and 2019. RESULTS: The average age of the patients was 11 years. A total of 100% of patients presented with bilateral uveitis, 50% had panuveitis and 92% had various choroidal involvement. Relevant information for diagnosis was provided in four patients. 5/12 had an abnormal 18F-FDG uptake. Of these, three patients had pathognomonic images of active granulomatous diseases. Three patients underwent PET CT-guided biopsies of which two were positive for sarcoidosis. CONCLUSION: 18F-FDG PET/CT provided important information for final diagnosis in approximately 30% (4/12) of pediatric patients with bilateral uveitis. Whole body FDG PET/ULD CT can contribute to the final diagnosis thanks to pathognomonic image of active granulomatous disease and/or by indicating metabolically active site of biopsy that would not be visualized in thorax CT.

Neurosyphilis cerebrospinal fluid findings in patients with ocular syphilis.

Purpose: To evaluate neurosyphilis cerebrospinal fluid (CSF) findings and initial ophthalmic manifestations in patients with syphilitic uveitis.Methods: We retrospectively reviewed the records of CSF analysis of 14 patients with syphilitic uveitis with treponemal analysis - chemiluminescent immunoassay and TPHA- and non-treponemal analysis - Rapid Plasma Reagin test - RPR.Results: 86% were males and 43% HIV+. Ocular signs of syphilis lead to the diagnosis of syphilis in 78% of patients. Typical syphilitic uveitis presentations included: acute syphilitic posterior placoid chorioretinitis (50% of patients), retinitis (21% of patients) and punctate inner retinitis (7% of patients). 57% of patients had definite neurosyphilis by the CDC criteria, while 71% had CSF abnormalities suggestive of central nervous system involvement.Conclusion: Based on international guidelines, the frequent CSF abnormalities found in syphilitic uveitis patient supports the diagnosis of neurosyphilis in a majority of patients.

ICAM-1 and VCAM-1 are differentially expressed on blood-retinal barrier cells during experimental autoimmune uveitis.

Adhesion molecules play a central role in leukocyte adhesion to the blood-retinal barrier (BRB) during uveitis. VCAM-1 expression on the BRB has been already described but although structurally similar, ICAM-1 has shown in various autoimmunity models to have distinct role and expression. Here, we induced uveitis in C57Bl/6 mice by adoptive transfer of semi-purified T cells from IRBP1-20-immunized mice. Using Flow cytometry analysis on transferred cells and immunofluorescence staining on retina we have studied the comparative ocular expression of both ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 at the surface of uveitogenic cells. Our results showed that LFA-1 and VLA-4 are expressed on both T and non T cells, VLA-4 sparsely and LFA-1 ubiquitously. Considering retinal expression, ICAM-1 is faintly present and VCAM-1 is absent in naive eyes. Only ICAM-1 is present on infiltrating cells in the retina and vitreous, while only VCAM-1 extends to perivascular glial cells and all along the internal limiting membrane. Finally, ICAM-1 is strongly expressed on the RPE, where VCAM-1 expression is much weaker. VCAM-1 seems most strongly expressed on the internal BRB while ICAM-1 predominates on the external BRB. Those major differences in the expression pattern could represent differential entry pathways for inflammatory cells to penetrate the eye.

Broncho-alveolar lavage (BAL) for the diagnosis of sarcoidosic uveitis.

PURPOSE: To evaluate the use of BAL for the diagnosis of sarcoidosic uveitis. METHODS: Retrospective study of 109 consecutive patients with uveitis and minimum 2 signs of ocular sarcoidosis who had a BAL and chest imaging. BAL(+) was defined as an alveolar (a) lymphocytosis (L) aL > 15% with aCD4/CD8 > 3.5. Serum angiotensin converting enzyme (sACE), tuberculin skin test and gallium scan were tested in 83, 95 and 24 patients. RESULTS: BAL was + in 26.6% of patients (86.2% females, mean age 50.8y) with mean aL = 46.8% and mean aCD4/CD8 = 8.5 which significantly differed form BAL(-) patients: 62.5% females, p < 0.02, mean age 43.6y, p < 0.05, mean aL = 17.2%, p < 0.001 and mean aCD4/CD8 = 1.8, p < 0.001. BAL(+) patients had 31% of bilateral hilar adenopathy (BHL(+)), and 59.1% of elevated sACE which significantly differed form BAL(-) patients: 8.8%, p = < 0.01 and 14.8% p < 0.001. CONCLUSION: Our findings suggest that BAL have a high diagnostic value and might be a useful additional test for the diagnosis of sarcoidosic uveitis, even with normal chest imaging.

Hyperosmotic stress induces cell cycle arrest in retinal pigmented epithelial cells.

Osmotic changes occur in many tissues and profoundly influence cell function. Herein, we investigated the effect of hyperosmotic stress on retinal pigmented epithelial (RPE) cells using a microarray approach. Upon 4-h exposure to 100 mM NaCl or 200 mM sucrose, 79 genes were downregulated and 72 upregulated. Three gene ontology categories were significantly modulated: cell proliferation, transcription from RNA polymerase II promoter and response to abiotic stimulus. Fluorescent-activated cell sorting analysis further demonstrated that owing to hyperosmotic stimulation for 24 h, cell count and cell proliferation, as well as the percentage of cells in G0/G1 and S phases were significantly decreased, whereas the percentage of cells in G2/M phases increased, and apoptosis and necrosis remained unaffected. Accordingly, hyperosmotic conditions induced a decrease of cyclin B1 and D1 expression, and an activation of the p38 mitogen-activated protein kinase. In conclusion, our results demonstrate that hypertonic conditions profoundly affect RPE cell gene transcription regulating cell proliferation by downregulation cyclin D1 and cyclin B1 protein expression.

Vitrectomy in uveitis patients.

PURPOSE: To evaluate the causes and success rates of pars plana vitrectomy (PPV) in uveitis patients. METHODS: Retrospective study of the charts of 26 uveitis patients (28 eyes) who underwent PPV between the years 2008 and 2011. We examined surgical indications and success rates, based on visual outcomes, complications and diagnosis in case of vitreous biopsy. RESULTS: (1) Therapeutic PPV (TV) was performed in 36% of the eyes, (2) TV combined with epiretinal membrane (ERM) peeling in 21% and (3) diagnostic PPV (DiV) was performed in 64% of the eyes. Eight eyes (28,6%) underwent a combined cataract and vitreous surgery. Visual acuity (VA) improved in 16 eyes (57%), with a mean improvement of -0,9 log of the minimum angle of resolution (logMAR), although the effect was transient in 7% of the cases. VA remained stable in 11 eyes (39%) and decreased in 1 (4%). Post-operative complications were cystic macular oedema (CMO) in 3 eyes (11%), cataract in 5 eyes (18%) and retinal detachment in 2 eyes (7%). Diagnostic tests were performed in 18 eyes with a success rate of 55%. CONCLUSIONS: In our series of patients with uveitis, a good andstable improvement of VA was found when PPV was performed with ERM peeling while the effect on VA was more transient in the other cases. A good success rate of diagnosis was also found in DiV. However, considering the possible severe complications, diagnostic vitrectomy should be limited to selected cases.

Characterization of retinal expression of vascular cell adhesion molecule (VCAM-1) during experimental autoimmune uveitis.

Leukocyte adhesion to the blood retinal barrier is a critical step in the pathogenesis of non-infectious uveitis and is mediated in part through the induction of adhesion molecules on retinal cells. Here, we have investigated the retinal expression of Vascular Cell Adhesion Molecule 1 (VCAM-1) in mouse experimental models of non-infectious uveitis. For each eyes, a histological score was given, and the expression of VCAM-1 analyzed by immunohistology. Co-labellings for GFAP, endoglin, aquaporin 4 and recoverin were also performed in order to determine which cell type expressed VCAM-1. In low grade uveitis, obtained after adoptive transfer of semi-purified autoreactive lymphocytes, VCAM-1 was only punctually expressed in the internal limiting membrane and epithelial cells of the ciliary body. Using the same adoptive transfer protocol, we found that, in correlation with disease severity, the staining extended to all internal limiting membranes, vasculitis lesions, Müller cell extensions, outer limiting membranes and RPE cells. VCAM-1 expression in the inner limiting membrane and Müller cell extensions co-stained with GFAP expression. In vasculitis lesions, VCAM-1 co-localized with either GFAP and endoglin expression. The labeling in the outer limiting membrane, did not exactly co-stained with AQ4 (Müller cells marker) or recoverin (photoreceptor marker) and the nature of this expression remained unexplained. Finally, VCAM-1 expression was also analyzed in classical experimental autoimmune uveitis eyes, and a similar pattern of expression was found. In conclusion VCAM-1 is expressed on all blood retinal barrier cells during experimental non-infectious uveitis and might thus play an important role in inflammatory cell recruitment during disease development.

Drug-induced uveitis in aids patients: two case reports.

Patients with acquired immunodeficiency syndrome (AIDS) can develop severe uveitis. Although infectious and autoimmune causes must always be considered, drug induced uveitis is also an important etiology. Herein, we present two case reports illustrating the classical presentation of rifabutin and cidofovir induced uveitis. The first case was a 33 year old woman with AIDS treated with anti-protease and anti-tuberculosis drugs (including rifabutin). She presented with a red painful right eye. There was a strong anterior segment inflammation with fibrinous exudates and a dense vitritis. Rifabutin was stopped and topical steroids and mydriatics were given. Intraocular inflammation and symptoms rapidly resolved. The second patient was a 36 year old woman who presented with a painful decrease of vision in her left eye. She was followed for bilateral CMV retinitis in the setting of AIDS and had recently received 2 systemic injections of cidofovir. Anterior segment inflammation with posterior synechiae in both eyes and folds of Descemet membrane in the left eye were noted. Intraocular pressure was 0 mmHg in the left eye and 10 mmHg in the right eye. Fundus examination disclosed CMV retinitis scars in the right eye and choroidal folds in the macula of the left eye. Cidofovir was discontinued and topical steroids and mydriatics started. Progressively the inflammation decreased and the intraocular pressure returned to normal levels. In conclusion, rifabutin and cidofovir are classical examples of drug induced uveitis with distinct characteristic clinical presentation. Recognition of those entities in AIDS patients can avoid useless and potentially invasive interventions in those fragile people.

[Post-streptococcal uveitis]. / Uvéites post-streptococciques.

PURPOSE: The role of streptococcal infections in the development of uveitis remains uncertain. Here we describe a series of patients with suspected poststreptococcal uveitis. OBSERVATION: Four retrospective cases were collected (two males and two females). All patients had a sore throat or an episode of pyrexia 2 to 10 weeks before the onset of uveitis and elevated antistreptolysin-O titer (ASOT); no other cause of uveitis was found. Uveitis was bilateral in all the cases and recurrent in only one. In two patients, inflammation was limited to the anterior segment. One patient had intermediate uveitis. One patient had posterior uveitis with multiple white-dot lesions as well as macular and optic disc swelling. The two cases with anterior uveitis were treated only topically and the two others received a short course of systemic steroids. No systemic antibiotics were given. CONCLUSIONS: These cases suggest that uveitis could be a manifestation of poststreptococcal syndrome and have a good prognosis.

Different presentations of ophthalmic aspergillosis.

PURPOSE: Aspergillus species is found worldwide and does not normally cause disease. However, when the immune system is compromised, it can invade many organs and be responsible for severe disease. The authors present cases with both classical and atypical features of ophthalmic aspergillosis. METHODS: Case series of three patients. RESULTS: All patients were female and had a long history of methylprednisolone use. The first two presented with endogenous endophthalmitis. One case was unilateral with a classical presentation of endophthalmitis. The other presented with a very severe bilateral acute retinal necrosis like syndrome. General work-up revealed disseminated disease in both cases. The diagnosis was made by serum immunologic testing in one case and after direct examination and culture from vitrectomy in the other. Despite intense antimycotic therapy, both patients died. The third patient presented with a unilateral progressive painful orbital apex syndrome. An orbital lesion was demonstrated by computed tomography scan and was unresponsive to methylprednisolone. Diagnosis of sino-orbital syndrome was made on biopsy. The lesion responded poorly to different antimycotic therapies, invaded the chiasma, and the patient lost all visual acuity. CONCLUSIONS: This case series illustrates that ophthalmic aspergillosis can present acutely with a devastating intraocular inflammation or more indolently in the setting of sino-orbital aspergillosis. Both forms have a poor visual prognosis and the systemic form is frequently associated with a fatal outcome.

CXCR4 expression in vitreoretinal membranes.

BACKGROUND/AIM: Proliferative vitreoretinopathy (PVR) and macular pucker (MP) vitreoretinal membranes are caused by abnormal cell migration. By their role in chemotactism, chemokine receptors represent good candidates to sustain this process. The authors thus investigated the expression of one of them, CXCR4, in these pathologies. METHODS: Three PVR and four MP membranes were surgically removed and processed for immunochemical studies with antibodies for CXCR4, cytokeratins or smooth muscle actin. RESULTS: CXCR4 expression was found in all membranes. There was no relation between severity of PVR or MP and presence of CXCR4. In addition, there was no difference in CXCR4 expression between MP and PVR. CONCLUSION: CXCR4 is expressed in PVR and MP. Further experiments are needed to test if CXCR4 and other chemokine receptors are implicated in vitreoretinal membrane formation.

Retinal pigment epithelial cells phagocytosis of T lymphocytes: possible implication in the immune privilege of the eye.

AIM: To investigate the capability of retinal pigment epithelium (RPE) cells to phagocytose T lymphocytes and to further analyse the immunobiological consequences of this phagocytosis. METHODS: Human RPE cells pretreated or not by cytochalasin, a phagocytosis inhibitor, were co-cultured with T lymphocytes for different time points. Phagocytosis was investigated by optic microscopy, electron microscopy, and flow cytometry. T cell proliferation was measured by (3)H thymidine incorporation. RPE interleukin 1beta mRNA expression was quantified by real time PCR. RESULTS: RPE cells phagocytose apoptotic and non-apoptotic T lymphocytes, in a time dependent manner. This is an active process mediated through actin polymerisation, blocked by cytochalasin E treatment. Inhibition of RPE cell phagocytosis capabilities within RPE-T cell co-cultures led to an increase of lectin induced T cell proliferation and an upregulation of interleukin 1beta mRNA expression in RPE cells. CONCLUSIONS: It is postulated that T lymphocyte phagocytosis by RPE cells might, by decreasing the total number of T lymphocytes, removing apoptotic lymphocytes, and downregulating the expression of IL-1beta, participate in vivo in the induction and maintenance of the immune privilege of the eye, preventing the development of intraocular inflammation.

Role and expression of CD40 on human retinal pigment epithelial cells.

PURPOSE: To examine the CD40 costimulatory molecule expression on normal resting or activated adult human retinal pigment epithelium (hRPE) cells and to evaluate its role as an activation molecule considering the potential antigen presentation functions of hRPE cells. METHODS: Expression of HLA-DR and costimulatory (CD40, B7.1, B7.2, CD54, and CD58) molecules on hRPE cells was analyzed by flow cytometry. CD40 triggering was performed using soluble CD40L or cocultures with CD40L transfected fibroblasts. Interleukin (IL)-6, -8, -10, and -12 secretions were measured by enzyme-linked immunosorbent assay. Antigen presentation function of hRPE cells was assessed by coculturing hRPE cells with allogeneic T cells. T-cell proliferation was measured by [(3)H]-thymidine incorporation, and T-cell apoptosis by measurement of caspase-3 activity. RESULTS: Interferon (IFN)gamma-activated hRPE cells expressed CD40, but not B7.1 or B7.2. Although interferongamma enhanced IL-6 and IL-8 production, CD40 triggering of IFNgamma-activated hRPE cells did not induce IL-12 secretion. hRPE cells did not stimulate allogeneic resting T cells and downregulated phytohemagglutinin-activated allogeneic T cells via a cell-to-cell contact-dependent mechanism. Some induction of apoptosis was detected. CONCLUSIONS: CD40 is expressed on IFNgamma-activated hRPE cells. Its ligation leads to an increased production of IL-6 and IL-8 but fails to induce B7.1 or B7. 2 expression, or to induce IL-12 secretion. Accordingly, hRPE cells do not activate allogenic T cells but inhibit T-cell proliferation, partly through induction of apoptosis. These results suggest that hRPE cells could be implicated more in a deviant antigen presentation. If the exact molecular mechanisms are unclear, it is likely that CD40-CD40L interaction could play a role in this process.