Laure Caspers

Comparison of Rubella Virus- and Herpes Virus-Associated Anterior Uveitis Clinical Manifestations and Visual Prognosis

PURPOSE To compare the clinical characteristics and visual prognosis of patients with anterior uveitis (AU) and intraocular fluid analysis positive for rubella virus (RV), herpes simplex virus (HSV), or varicella zoster virus (VZV). DESIGN Retrospective, observational study. PARTICIPANTS The study included 106 patients with AU and positive polymerase chain reaction (PCR) results, Goldmann-Witmer coefficients (GWCs), or both, for RV (n = 57), HSV (n = 39), or VZV (n = 10). METHODS Clinical records of the included patients were analyzed retrospectively; demographic constitution, ophthalmologic characteristics, and visual prognosis were compared. MAIN OUTCOME MEASURES Age, gender, and diverse clinical and laboratory characteristics, including course and laterality of AU; prevalence of positive results for PCR, GWC, or both; conjunctival redness; corneal edema; history of keratitis; presence of keratic precipitates; synechiae; heterochromia; and grade of inflammation. In addition, complications and visual acuity at 1 and 3 years of follow-up were recorded. RESULTS All 3 types of viral AU were characterized by unilateral involvement (80%-97%). Rubella virus AU was characterized by younger age at onset and chronic course and typically was associated with cataract at presentation. Heterochromia was present in 23% of RV AU patients. Anterior uveitis associated with HSV or VZV occurred characteristically in older patients and frequently followed an acute course. Clinical features associated with herpetic AU included conjunctival redness, corneal edema, history of keratitis, and development of posterior synechiae. Herpes simplex virus AU often had severe anterior chamber inflammation, whereas the presence of vitritis was more common in RV AU and VZV AU. The prevalence of documented intraocular pressure (IOP) of more than 30 mmHg (25%-50%; P = 0.06) and development of glaucoma (18%-30%; P = 0.686) were similar in all 3 groups. Focal chorioretinal scars were seen in 22% of RV AU eyes, in 0% of HSV AU eyes, and in 11% of VZV AU eyes (P = 0.003). Visual prognosis was favorable for all 3 groups. CONCLUSIONS These observations identify clinical differences between RV AU, HSV AU, and VZV AU and may be of particular value to ophthalmologists who are unable to carry out intraocular fluid analysis to discriminate between these types of viral AU. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Endogenous endophthalmitis complicating Klebsiella pneumoniae liver abscess in Europe: case report

Purpose: To report the first European case of endogenous endophthalmitis secondary to a liver abscess due to Klebsiella pneumoniae expressing MagA gene. Methods: A 33-year-old diabetic patient was admitted for fever and right upper quadrant abdominal pain. Abdominal computed tomography and laboratory studies were performed. On day 4 after admission, patient complained of a painful and red right eye with decreased vision. A complete ophthalmological examination, including visual acuity assessment, slit lamp examination and fundus ophthalmoscopy was started. Results: Klebsiella pneumoniae liver abscess was diagnosed and antibiotherapy initiated. Polymerase chain reaction revealed that the isolated Klebsiella pneumoniae was serotype K1 and positive for Mag A. Ophthalmological examination disclosed cells in the anterior chamber and an important vitritis. Fundus was barely visible. A diagnosis of Klebsiella pneumoniae endogenous endophthalmitis complicating liver abscess was made. Intravitreal injection of antibiotics resulted in a preservation of visual acuity. Conclusion: This report suggests that rather than being confined to Taiwan, endogenous endophthalmitis secondary to a liver abscess due to Klebsiella pneumoniae expressing MagA gene, is becoming a global problem.

Uveitis-like syndrome and iris transillumination after the use of oral moxifloxacin.

ObjectiveTo report a newly recognized adverse effect of oral moxifloxacin.DesignObservational case reports.ParticipantsFive patients who used oral moxifloxacin therapy.Main outcome measuresIn five patients, a uveitis-like episode followed oral moxifloxacin therapy, afterwards they experienced photophobia. At slitlamp investigation, the patients showed almost complete iris transillumination, not restricted to one sector, and persistent mydriasis of the pupil, with no reaction to light and no near reflex. Follow-up of 3 years in one of the patients showed no change of symptoms. Only in one patient, with a history of anterior uveitis, an anterior chamber tap was positive for herpes simplex genome. Only after the use of moxifloxacin did she experience continuous photophobia.ConclusionsIris transillumination and sphincter paralysis is a newly recognized adverse effect of oral moxifloxacin therapy.

Photodynamic therapy for subfoveal classic choroidal neovascularization related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like)

Purpose: To evaluate the safety and efficacy of photodynamic therapy with verteporfin (PDT) for subfoveal classic choroidal neovascularization (CNV) related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like). Methods: Retrospective review of 16 eyes from 14 patients with subfoveal classic CNV associated with PIC or POHS-like and treated with PDT. Results: The mean visual acuity increased from 4.5/10 (range: 1/10–9/10) to 7/10 (range: 2/10-10/10) after a mean follow-up of 21 months (range: 8–32 months) and a mean number of 2 PDT (range: 1–6). Visual acuity remained stable or improved in 13 of the 16 eyes (81%) and decreased in three. Conclusion: This nearly two-year follow-up study suggests that PDT could be helpful for patients with subfoveal classic CNV related to PIC or POHS-like.

Extracellular Nucleotides and Interleukin-8 Production by ARPE Cells: Potential Role of Danger Signals in Blood–Retinal Barrier Activation

PURPOSE RPE cell activation is an important feature of autoimmune uveitis. This investigation focused on whether extracellular nucleotides could contribute to this activation, and the effects of ATPgammaS, UTP, and UDP on the production of IL-8 by RPE cells was studied in relation to their expression of functional P2Y receptors. METHODS ARPE-19 cells were cultured with ATPgammaS, UTP, UDP, and TNF. IL-8 gene transcription and protein production were measured by semiquantitative RT-PCR and ELISA. Western blot analysis and RT-PCR were used to investigate ERK 1/2 activation and P2Y expression. Changes in intracellular calcium and cAMP concentration were analyzed by spectrofluorometry and radioimmunoassay. RESULTS Stimulation of ARPE-19 cells with ATPgammaS, UTP, and UDP induced IL-8 gene transcription and protein secretion. TNFalpha induction of IL-8 secretion was also increased by ATPgammaS, UTP, and UDP. Nucleotide induction of IL-8 production was blocked by PD98059, and all nucleotides stimulated ERK 1/2 phosphorylation. P2Y(2) and P2Y(6) mRNAs were detected in ARPE-19 cells. All tested nucleotides induced a pulse of intracellular calcium. CONCLUSIONS ATPgammaS, UTP, and UDP stimulate both basal and TNFalpha-induced IL-8 secretion in RPE cells through an ERK 1/2-dependent pathway. The results suggest that those effects are mediated by P2Y(2) and P2Y(6) receptors.

Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells.

The retinal pigmented epithelium (RPE) is composed of retinal pigmented epithelial cells joined by tight junctions and represents the outer blood-retinal barrier (BRB). The inner BRB is made of endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows the osmotic gradient and flows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins, and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy incriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools.

Rifabutin-Associated Panuveitis with Retinal Vasculitis in Pulmonary Tuberculosis

Introduction: Rifabutin-associated uveitis has been reported frequently in AIDS patients and more rarely in immunocompetent patients. It is characterized clinically by anterior acute uveitis. Only a few poorly documented cases of rifabutin-induced panuveitis with retinal vasculitis have been reported. Here, we report four cases of rifabutin-associated panuveitis with retinal vasculitis. Case reports: We describe four patients with active tuberculosis, treated with a multidrug regimen including rifabutin for at least 1.5 months before presentation. The first patient was immunocompetent, the three others had AIDS and were undergoing triple anti-HIV therapy. Three patients were women with a low body weight. All four patients presented with panuveitis and retinal vasculitis. Interruption of the drug rapidly reduced the ocular inflammation in all cases. Conclusion: Four cases of rifabutin-associated panuveitis with retinal vasculitis are reported in patients with active pulmonary tuberculosis. Immunogenicity of Mycobacterium tuberculosis as well as the very low weight of the patients might be implicated in the development of this unusual form of rifabutin-associated uveitis.

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.

Severe bilateral panuveitis during melanoma treatment by Dabrafenib and Trametinib

BackgroundWe report a case of severe bilateral panuveitis during melanoma therapy with a combination of Dabrafenib, a B-raf (BRAF) inhibitor, and Trametinib, a mitogen/extracellular signal-regulated kinase (MEK) inhibitor. Both of these drugs are effectors in the mitogen-activated protein kinase (MAPK) pathway, which plays an important role in the physiopathology of melanoma. Dabrafenib and Trametinib have shown improved survival of patients with metastatic melanoma but they have also been associated with the development of uveitis.FindingsOur patient was a 55-year-old woman with metastatic melanoma who presented with sudden onset of bilateral painless visual loss. She had been treated with Dabrafenib and Trametinib. Trametinib was discontinued at the onset of symptoms but there was no improvement. Ophthalmological examination revealed severe bilateral non-granulomatous panuveitis, with choroidal thickening, chorio-retinal folds, and multiple serous retinal detachments (SRDs). Topical corticosteroid treatment was initiated, and Dabrafenib was discontinued. A good response was obtained with a recovery of visual acuity of 20/25 on both eyes and an almost complete resolution of the SRDs.ConclusionsThis case highly suggests that MAPK pathway inhibition can lead to severe uveitis. Dabrafenib and Trametinib could have both played a role in inducing the disease. Further studies are needed to evaluate the possible role of the combination of these drugs in inducing uveitis and SRD.

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.