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.

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.

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.

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.

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.

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.

[Lyme disease from an ophthalmological point of view]. / La maladie de Lyme du point de vue de l'ophtalmologue.

The first case of Lyme disease was described more than 25 years ago in the city of Lyme, Connecticut (USA) and although the responsible pathogenic organism is known (Borrelia Burgdorferi) as well as its vector (a tick from the Ixode genus), it is still underdiagnosed and often poorly known by practitioners. The symptomatology is classically divided into three phases depending on the time between the tick bite and the first symptoms. However, in a number of cases this clinical division of the disease is not easily applied. We describe three cases of atypical ocular manifestations to illustrate this problem. Recently developed laboratory tests help confirm the diagnosis but should not be used without a good knowledge of the disease. This study aims to emphasize the difficulty of diagnosis and the importance of appropriate treatment and to avoid potentially permanent complications.

Vitrectomy and silicone oil in the treatment of acute endophthalmitis. Preliminary results.

PURPOSE: To evaluate the role of pars plana vitrectomy (PPV) and silicone oil injection in the treatment strategy of severe endophthalmitis. PATIENTS AND METHODS: This study analyses a retrospective case series of 34 patients with signs and symptoms of severe endophthalmitis with visual acuity limited to light perception. All underwent PPV with intraocular injection of antibiotics (IOAB), together with topical and oral antibiotics. In 10 patients (group 1), this treatment alone was sufficient to control infection. In 10 other patients (group 2) with the same initial treatment, a new vitrectomy was needed: 8 because of retinal detachment, 2 because of persistent infection. In 2 patients (group 3), initially treated with PPV and IOAB, a second vitrectomy with IOAB and silicone oil tamponade was needed to stop infection. In 12 patients (group 4), with the worse prognosis related to the severity of infection and/or to associated retinal necrosis, PPV, IOAB and silicone oil tamponade were conducted at first surgery. Final anatomic status and visual acuity were assessed to compare the effectiveness of these different treatments. RESULTS: In 22 patients (group 1, 2 and 3) treated initially without silicone oil, 12 patients (55%) needed further surgery, either for persistent infection or retinal detachment. Twelve patients (group 4) treated at first with silicone oil had a rapid control of the infectious process and better anatomical results with this procedure only. Final visual acuity was also better in the silicone oil groups (group 3 and 4) than in the non silicone groups (group 1 and 2). CONCLUSION: These results suggest that silicone oil tamponade might be beneficial in the treatment strategy of severe endophthalmitis.

[Atypical Cogan's syndrome. Based on a case]. / Le syndrome de Cogan atypique. A propos d'un cas.

Cogan's syndrome is a systemic inflammatory disease that associates typical (interstitial keratitis) and atypical (such as anterior uveitis) ocular manifestations to vestibulo-auditory dysfunction. It has also a systemic vascular association of vasculitis type. We report a case of a 64 years old woman who presented an atypical form with anterior uveitis.

[Impact of anti-retroviral treatment with protease inhibitors on the evolution of cytomegalovirus retinitis in the patient carrying acquired immunodeficiency syndrome]. / Impact du traitement anti-rétroviral par inhibiteurs des protéases sur l'évolution de la rétinite à cytomégalovirus chez le patient porteur du syndrome d'immunodéficience acquise.

Up to now cytomegalovirus retinitis (CMVR) recurrence in AIDS patients was considered to be very high, even on maintenance therapy. Protease inhibitors (PI) are antiretroviral molecules which, with more efficacity than reverse transcriptase inhibitors, decrease viral charge and increase CD4's count aswell as survival. We analysed the impact of PI on CMVR evolution in a retrospective review of 18 patients with CMVR on maintenance therapy and PI treatment. In a first group, 13 patients started PI some time after CMVR diagnosis (median CD4 = 9/mm3). A second group of 5 patients developed CMVR (median CD4 = 63/mm3) after initiation of PI. In the first group, incidence of CMVR recurrences/1000 patients days was 6,45 (2323 patients days of follow-up (PDFU) before starting PI and 3,44 (4066 PDFU) after starting PI. In this group, during the follow-up's period of CD4's count inferior to 75/mm3, incidence of CMVR is 6,84/1000 patients days and becomes 0,86/1000 patients days during the follow-up's period of CD4's count superior to 75/mm3. In the second group, incidence of CMVR was 0/1000 patients days (1972 PDFU). In summary, incidence of CMVR decreases with PI's treatment. Interruption of CMVR maintenance therapy could be considered in patients with CD4's count higher than 75/mm3.

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.

Proliferative diabetic retinopathy in long-term diabetic patients with and without clinical osteoarthritis.

OBJECTIVE: To determine whether some long-term diabetic patients with coexisting clinical osteoarthritis (OA) are less likely to develop diabetic retinopathy (DR) than other diabetic patients and whether there is a relation between the timing of the clinical OA onset and DR. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case-control study of 85 osteoarthritic patients with 20 years or more diabetes (A/DM) control group and of 85 non-osteoarthritic diabetic patients (NoA/DM) matched for age, race, duration, and type of diabetes. Digital fundus photographs were graded for retinopathy in masked manner. RESULTS: Glycosylated hemoglobin, hypertension, and smoking showed no significant difference. Twelve out of 85 patients (12.9%) in A/DM group developed proliferative diabetic retinopathy (PDR) whereas 79/85 (92.9%) NoA/DM patients developed PDR (P<0.001). The onset of OA symptoms was known in 80/85 of the A/D patients, including 47 patients with onset before or at the same year as DM and 33 patients with relative onset after the year of DM. All the 10 patients with PDR (10/33) developed OA subsequent to their initiation for diabetic treatment while 0/47 A/DM patients with the onset of osteoarthritic symptoms present before or the same year as their onset of diabetes developed PDR (P<0.001). CONCLUSION: Our study suggests that in long-term DM, PDR was significantly associated with the absence of concomitant clinical OA. This observation was highly significant if the onset of the arthritis was the same year or before the onset of the diabetes.

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.

[Toxoplasmic chorioretinitis: positive PCR on vitreous with negative serology for Toxoplasma gondii]. / Choriorétinite toxoplasmique : PCR positive du vitré malgré une sérologie négative pour Toxoplasma gondii.

Ocular recurrences of congenital toxoplasmosis usually occur during the first and second decades of life. At that time, serum levels of IgG against toxoplasmosis are almost always detectable because of the very high sensitivity of the test. The diagnosis is mainly supported by the ophthalmological examination and the good clinical response to treatment. In atypical cases, the Goldman-Witmer coefficient (GWC) on aqueous and polymerase chain reaction (PCR) on aqueous or vitreous is usually performed to substantiate the diagnosis. We report a case of recurrent macular chorioretinitis in a 13-year-old immunocompetent patient with a history of congenital toxoplasmosis whose repeated serologies remained negative or uncertain. However, the diagnosis of toxoplasmic chorioretinitis was supported by the detection of Toxoplasma gondii DNA by PCR analysis in a vitreous sample. Although the sensitivity of serology is very high, it is not perfect and there are false-negative results. In case of high clinical presumption in spite of a negative serology, PCR could be a helpful contribution to the diagnosis.

[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.

The effect of centrifugal accelerations on the polarity of statocytes and on the graviperception of cress roots.

The structural polarity of statocytes of Lepidium sativum L. is converted to a physical stratification by a root-tip-directed centrifugal acceleration. Sedimentation of amyloplasts and nucleus to the centrifugal (distal) cell pole and the lateral displacement of the distal endoplasmic reticulum (ER) complex occur after centrifugation for 20 min at an acceleration of 50 g. With higher doses (20 min, 100-2,000 g), smaller organelles become increasingly displaced. From the centrifugal to the centripetal cell pole, the following stratification is observed: 1) amyloplasts with mitochondria; 2) nucleus with mitochondria and a few dictyosomes, as well as laterally located ER; 3) dictyosomes with a few mitochondria; 4) vacuoles; and 5) lipid droplets. Within the first 7.5 min, after the roots have been returned to 1 g, the original arrangement of the amyloplasts sedimented on the underlying ER complex is reestablished in 66% of the statocytes. When roots previously centrifuged in an apical direction are exposed in a horizontal position to 1 g, the latent period of the graviresponse is increased by 7.5 min relative to the non-centrifuged controls. The kinetics of the response are identical to the controls. Roots centrifuged first in an apical direction and then for 2 h in a lateral direction (1,000 g) have statocytes with a physical stratification perpendicular to the root axis. A gravitropic curvature does not take place during the lateral centrifugation. These results support the hypothesis that the distal ER complex is necessary and sufficient for graviperception.