Ann-Marie Lobo

Pathogenesis of herpes simplex keratitis: The host cell response and ocular surface sequelae to infection and inflammation

Herpes simplex virus type 1 (HSV) keratitis is a leading cause of infectious blindness. Clinical disease occurs variably throughout the cornea from epithelium to endothelium and recurrent HSV stromal keratitis is associated with corneal scarring and neovascularization. HSV keratitis can be associated with ocular pain and subsequent neutrophic keratopathy. Host cell interactions with HSV trigger an inflammatory cascade responsible not only for clearance of virus but also for progressive corneal opacification due to inflammatory cell infiltrate, angiogenesis, and corneal nerve loss. Current antiviral therapies target viral replication to decrease disease duration, severity and recurrence, but there are limitations to these agents. Therapies directed towards viral entry into cells, protein synthesis, inflammatory cytokines and vascular endothelial growth factor pathways in animal models represent promising new approaches to the treatment of recurrent HSV keratitis.

Association between eye diagnosis and positive syphilis test results in a large, urban sexually transmitted infection/primary care clinic population

In 2015, the Centers for Disease Control and Prevention (CDC) and the American Academy of Ophthalmology (AAO) released clinical advisories on rising cases of ocular syphilis. We examined the association between eye disease and syphilis infection among primary care and sexually transmitted infection (STI) clinic patients attending an urban lesbian, gay, bisexual, transgender (LGBT) health center. We conducted a retrospective medical record review of all patients who underwent syphilis testing at Howard Brown Health between 1 January 2010 and 31 December 2015. Confirmed eye diagnosis was based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes for conjunctivitis, uveitis, keratitis, retinitis, and red eye. Demographic information, syphilis treatment, HIV status, and high-risk behaviors were abstracted. Syphilis diagnosis was defined by available laboratory data (enzyme immunoassay [EIA], rapid plasma reagin [RPR] titer, fluorescent treponemal antibody absorption [FTA-Abs], Treponema pallidum Ab). Multivariable logistic regression with robust variance was used to identify independent associations. During the study period, 71,299 syphilis tests were performed on 30,422 patients. There were 2288 (3.2%) positive syphilis tests. Seventy-seven patients had a confirmed eye diagnosis (0.25%). Patients with eye disease had higher probability of at least one positive syphilis test (33%) compared to those without eye disease (8%) (pu2009<u20090.01). Of patients with eye disease, 77% were men who had sex with men (MSM) and 65% were HIV-positive. Patients with eye disease had 5.97 (95% CI: 3.70, 9.63) higher odds of having syphilis compared to patients without eye disease. When adjusted for age, race, gender/sexual orientation, insurance status, and HIV status, this association between positive syphilis test and eye disease decreased but was still significant (OR 2.00, 95% CI 1.17, 3.41). Patients who present with an eye diagnosis to STI/primary care clinic have a higher probability of positive syphilis tests even after adjusting for other risk factors for syphilis. High-risk patients with eye symptoms should have routine STI testing and in keeping with CDC and AAO recommendations, full ophthalmologic examination.

Pre-papillary vitreous opacities associated with Behçet’s disease: a case series and review of the literature

PurposeTo present pre-papillary vitreous opacity as an uncommon manifestation of inflammation in Behçet’s disease that may be specific to this uveitic entity.MethodsWe retrospectively reviewed the charts of 67 patients with Behçet’s disease examined at our clinic between 2005 and 2016. Behçet’s disease was diagnosed based on established clinical criteria of inflammation involving the eyes, mucocutaneous junctions, and skin. Patients with Behçet’s disease who presented with papillitis and a pre-papillary vitreous opacity were identified. Response to anti-inflammatory treatment on examination and optical coherence tomography imaging were evaluated. PubMed searches were performed for (1) other cases with pre-papillary vitreous opacities in uveitic entities and (2) reports of optic nerve involvement specifically in Behçet’s disease.ResultsWe identified three patients with Behçet’s disease who presented with unilateral papillitis and a pre-papillary vitreous opacity. The pre-papillary vitreous opacity had a funnel-shaped appearance on optical coherence tomography. All patients were initially treated with steroids, which led to resolution of the opacity clinically and on imaging. We identified one previous report of such a pre-papillary opacity in a patient with Behçet’s disease, and no reports of this finding in other uveitic entities.ConclusionThis study expands the number of Behçet’s disease cases presenting with a pre-papillary vitreous opacity and demonstrates novel optical coherence imaging of this finding. This finding may be specific to Behçet’s disease as it was not identified in other uveitic entities in a review of the existing literature.

Endophthalmitis in Immunocompromised and Diabetic Patients

Endophthalmitis is a serious condition in immunocompromised patients. Exogenous endophthalmitis that develops in the setting of ocular surgery, trauma, and corneal infections also occurs in immunocompromised hosts, sometimes more frequently than in immunocompetent individuals. More importantly, immunocompromised patients are at increased risk of developing endogenous endophthalmitis due to their weakened immune defense and susceptibility to bacteremia and fungemia. Endogenous fungal endophthalmitis is of particular concern because fungemia has a high mortality in this patient population. The diagnosis of endogenous endophthalmitis is suspected clinically, and antibiotics are often started empirically as soon as blood cultures are drawn. Intravitreal antibiotics, systemic antibiotics, and vitrectomy are utilized in combination based on the infection severity and response to initial treatments. Prognosis is variable depending on the virulence of the organism and the severity of the intraocular inflammation. In patients with HIV/AIDS, endophthalmitis is relatively rare compared with other ocular diseases. Patients with HIV who are intravenous drug users are at increased risk of endogenous endophthalmitis, and in these cases, fungal pathogens such as Candida and Aspergillus are the most common etiologies. In transplant patients on immunosuppressive therapies, endophthalmitis is also most commonly fungal, and pathogens include Candida, Aspergillus, Scedosporium, and Fusarium. Patients with rheumatologic conditions receiving immunosuppressive medications and patients with hematologic malignancies or asplenia are also at increased risk for endophthalmitis, either bacterial or fungal.

NOD2 genetic variants and sarcoidosis-associated uveitis

Purpose Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood. We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. Methods In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the NOD2 gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NOD2 NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test. Results There were no significant differences in NOD2 common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic NOD2 mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn’s disease and psoriatic arthritis. Conclusions Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic NOD2 variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms.