Objective Quantification of Anterior Chamber Inflammation: Measuring Cells and Flare by Anterior Segment Optical Coherence Tomography.

PURPOSE: To assess the ability of swept-source (SS) optical coherence tomography (OCT) of the anterior segment (AS) to measure anterior chamber (AC) inflammation (both flare and cells) objectively. To compare OCT-derived inflammatory indices with standard techniques. DESIGN: Prospective evaluation of a diagnostic test. PARTICIPANTS: Patients diagnosed with anterior uveitis (active or inactive) and controls. METHODS: Participants underwent an AC inflammation evaluation including: clinical cell and flare grading and laser flare photometry (LFP). Uveitis patients were divided into active or inactive uveitis status according to clinical grading. Anterior segment SS-OCT scans were obtained for each participant. Tomographic images were analyzed to count the AC cells, and to calculate to absolute measurements of aqueous signal intensity. The absolute values were compared with the signal measured by the scan outside the eye, generating an optical density ratio (aqueous-to-air relative intensity [ARI] index). Correlations between OCT-derived AC inflammatory indexes and LFP, clinical grading, participant category (active or inactive uveitis, control), age, gender, and central corneal thickness (CCT) were assessed. MAIN OUTCOME MEASURES: Correlation between OCT-derived AC inflammatory indexes (ARI index and AC cells on OCT) and standard clinical techniques (LFP, clinical cell grading). RESULTS: Two hundred thirty-seven eyes (70 active uveitis, 97 inactive uveitis, and 70 controls) were included. Anterior chamber cells count on OCT did not differ between inactive uveitis and controls, but was significantly higher in active uveitis compared to the other categories (both P < 0.0001). All groups had different LFP (all P < 0.0001). Active uveitis had significantly higher ARI index compared with inactive uveitis and controls (both P < 0.0001). Interobserver agreement (intraclass correlation coefficient) for ARI index was 0.78. The ARI index correlated positively with age (P = 0.043) and negatively with CCT (P = 0.006). The ARI index correlated with LFP in the active uveitis group (P < 0.0001), but not in the others. Anterior chamber cells on OCT increased among all cell clinical grades (P < 0.0001). The ARI index increased among all flare clinical grades (P < 0.005). CONCLUSIONS: Anterior segment SS-OCT could be used for a comprehensive assessment of AC inflammation, providing objective measurements of inflammatory cells and aqueous flare.

Interaction of non-human primate complement and antibodies with hypermucoviscous Klebsiella pneumoniae.

Emergent hypermucoviscosity (HMV) phenotypes of Klebsiella pneumoniae have been associated with increased invasiveness and pathogenicity in primates. In this study, we investigated the interaction of African green monkeys (AGM) (Chlorocebus aethiops sabaeus) complement and antibody with HMV and non-HMV isolates as in vitro models of primate infection. Significantly greater survival of HMV isolates was evident after incubation in normal serum or whole blood (p < 0.05) of AGM donors when compared to non-HMV strains. Greater survival of HMV strains (p < 0.05) was found after incubation in whole blood and serum from seropositive donors when compared to seronegative donor samples. Additionally, significantly greater amounts of K. pneumoniae were phagocytozed by AGM leukocytes when complement was active (p < 0.05), but no difference in uptake was observed when serum from seropositive or seronegative animals was used in challenged cells utilizing flow cytometry. Results demonstrate that interaction of cellular and humoral immune elements play a role in the in vitro killing of K. pneumoniae, particularly HMV isolates. Neither AGM serum, nor washed whole blood effectively killed HMV isolates; however, assays using heparinized whole blood of seronegative donors significantly reduced viability of HMV and non-HMV strains. The lack of bacterial killing observed in seropositive donors treatments could be at least partially associated with low IgG2 present in these animals. A better understanding of the pathogenesis of klebsiellosis in primates and host immune response is necessary to identify surface molecules that can induce both opsonizing and bactericidal antibody facilitating killing of Klebsiella, and the development of vaccines in human and animals.

Interferon Alpha-2a for the Treatment of Post-Infectious Uveitis Secondary to Presumed Intraocular Tuberculosis.

Purpose: To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB). Methods: Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months. Results: Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months (p = 0.03). Mean CRT decreased from 372 ± 132.2 µm to 274.66 ± 34.9 µm at six months (p = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded. Conclusions: IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB.

Vitreoretinal lymphomas misdiagnosed as uveitis: Lessons learned from a case series.

PURPOSE: To present challenging cases of vitreoretinal lymphoma (VRL) that was misdiagnosed as uveitis because of the apparent intraocular inflammation. At the light of the new classification of intraocular lymphomas, we detail the characteristics that masqueraded the tumors and the clinical aspects that guided us to the correct diagnosis. MATERIALS AND METHODS: We retrospectively reviewed the patients referred to our uveitis service between January 2006 and December 2014. RESULTS: Seven patients referred with a presumptive diagnosis of idiopathic uveitis received a final diagnosis of VRL. The median time between the onset of symptoms and definitive diagnosis was 25 months for these complex cases. The median time from presentation at our clinic to final diagnosis was 1 month. The described clinical features including dense vitreous cells and subretinal infiltrates were characteristic and tend to be present in all these chronically ill patients. Vitreous samples were collected, and all demonstrated the pathognomonic tumor cells, the specific immunoglobulin heavy chain gene rearrangements, and an interleukin (IL)-10 to IL-6 ratio >1. CONCLUSION: VRLs are severe diseases with a poor prognosis that may be misdiagnosed as idiopathic inflammatory conditions of the eye. Treatment with steroids may occult the tumors and delay the correct diagnosis. Appropriate evaluation may prompt to a timely vitreous sampling and therefore to a faster diagnosis in these peculiar cases where the correct diagnosis was delayed by several months.

Unusual presentation of pediatric acute sphenoid sinusitis.

BACKGROUND: Sphenoid sinus lesions are rare entities, occurring in 2 - 3% out of all paranasal sinus lesions. Isolated oculomotor nerve palsy due to acute sphenoid sinusitis is very rare, with only few cases reported in literature. METHODS: Retrospective report about a case of isolated acute sphenoid sinusitis in a child with a left-sided third cranial nerve paralysis as the only sign at presentation. RESULTS: Isolated oculomotor nerve palsy can be the initial sign of an isolated acute sphenoid sinusitis in children and it requires a high index of suspicion in order to avoid a delay in diagnosis. CONCLUSIONS: Magnetic resonance imaging should be promptly performed. Functional endoscopic sinus surgery represents the treatment of choice in order to restore sinus drainage and avoid further intracranial or ocular complications. The need of serial postoperative debridement under general anesthesia should be adequately scheduled and previously discussed with parents.

Evaluation of prostaglandin analogue effects on corneal keratocyte density using scanning laser confocal microscopy.

PURPOSE: To determine if treatment with prostaglandin (PG) analogues affects keratocyte density as an indirect measure of extracellular matrix in the corneal stroma. PATIENTS AND METHODS: In this case control study, 129 eyes from 68 patients were examined: 52 eyes had only PG analogue therapy for at least 3 years, 37 eyes had only ß-adrenergic blocker therapy for at least 3 years, and 40 control eyes were without therapy. Scanning laser confocal microscopy was carried out, and each corneal stroma was subdivided into the anterior, midstroma, and posterior stroma. Keratocyte density was determined from the images by manual counting. RESULTS: Keratocyte densities in the entire stroma and in 2 stromal layers were significantly higher in patients with PG analogue therapy compared with control patients (entire stroma, P<0.001; anterior stroma, P=0.001; posterior stroma, P=0.016). Keratocyte density in the PG analogue therapy patients was also greater compared with the ß-adrenergic blocker patients (entire stroma, P<0.001; anterior stroma, P<0.001; mid-stroma P=0.023, posterior stroma P=0.007). There were no significant differences between the control and ß-adrenergic blocker groups. Overall, the density increase for the PG analogue group was greatest in the anterior stroma. CONCLUSIONS: PG analogue therapy increased the keratocyte density in each layer of corneal stroma, but more significantly in the anterior stroma than in the midstroma or the posterior stroma. The increased keratocyte density might be the result of diminished extracellular matrix, possibly owing to the known activation of matrix metalloproteinases and inhibition of tissue inhibitors of the metalloproteinases.