Person:

Eliott, Dean

Endogenous endophthalmitis (EE) is a rare but devastating infection that occurs secondary to seeding of the intraocular cavity from an extraocular focus. Recent reports suggest the increasing prevalence and incidence of Klebsiella pneumoniae as a causative organism in Asian countries. Analysis of the largest cohorts published to date suggests that K. pneumoniae endogenous endophthalmitis (KPEE) is 10 to 15 times more prevalent than other causes of EE. The incidence of KPEE among patients with systemic Klebsiella infection appears to be >100-fold more common than other causes of EE. The exact reason for these observations is not clear, but a number of studies now suggest that Klebsiella serotypes K1 and K2 have virulence factors that enhance their survival in diabetic patients and increase their pathogenicity. Here, we report two cases of KPEE in the USA. We also review the recent clinical and basic science literature on the prevalence, incidence, and pathophysiology of this emerging and devastating infection.

Silicone oil continues to be an important aid in retinal detachment surgery. We report a case in which disparate responses to silicone oil were noted in the conjunctiva and intraocularly. Intraocularly, the oil permeated a fibrous membrane that formed behind a keratoprosthesis, the first example of this phenomenon. We detail the histological response to the oil at this site as well as a distinctly different reaction present to oil in the conjunctiva of the same eye. The divergence of histological responses provides a demonstration of the eye's apparent retained capacity to protect against intraocular inflammation, despite multiple previous surgeries.

Background: Biomarker”, a merged word of “biological marker”, refers to a broad subcategory of medical signs that objectively indicate the state of health, and well-being of an individual. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases. Main body Spectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints. Conclusion: OCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.

Purpose Epiretinal fibrovascular membranes (FVMs) are a hallmark of proliferative diabetic retinopathy (PDR). Surgical removal of FVMs is often indicated to treat tractional retinal detachment. This potentially informative pathological tissue is usually disposed of after surgery without further examination. We developed a method for isolating and characterizing cells derived from FVMs and correlated their expression of specific markers in culture with that in tissue. Methods: FVMs were obtained from 11 patients with PDR during diabetic vitrectomy surgery and were analyzed with electron microscopy (EM), comparative genomic hybridization (CGH), immunohistochemistry, and/or digested with collagenase II for cell isolation and culture. Antibody arrays and enzyme-linked immunosorbent assay (ELISA) were used to profile secreted angiogenesis-related proteins in cell culture supernatants. Results: EM analysis of the FVMs showed abnormal vessels composed of endothelial cells with large nuclei and plasma membrane infoldings, loosely attached perivascular cells, and stromal cells. The cellular constituents of the FVMs lacked major chromosomal aberrations as shown with CGH. Cells derived from FVMs (C-FVMs) could be isolated and maintained in culture. The C-FVMs retained the expression of markers of cell identity in primary culture, which define specific cell populations including CD31-positive, alpha-smooth muscle actin-positive (SMA), and glial fibrillary acidic protein-positive (GFAP) cells. In primary culture, secretion of angiopoietin-1 and thrombospondin-1 was significantly decreased in culture conditions that resemble a diabetic environment in SMA-positive C-FVMs compared to human retinal pericytes derived from a non-diabetic donor. Conclusions: C-FVMs obtained from individuals with PDR can be isolated, cultured, and profiled in vitro and may constitute a unique resource for the discovery of cell signaling mechanisms underlying PDR that extends beyond current animal and cell culture models.

Purpose The purpose of this study was to develop a method for isolating, culturing, and characterizing cells from patient-derived membranes in proliferative vitreoretinopathy (PVR) to be used for drug testing. Methods: PVR membranes were obtained from six patients with grade C PVR. Membrane fragments were analyzed by gross evaluation, fixed for immunohistologic studies to establish cell identity, or digested with collagenase II to obtain single cell suspensions for culture. PVR-derived primary cultures were used to examine the effects of methotrexate (MTX) on proliferation, migration, and cell death. Results: Gross analysis of PVR membranes showed presence of pigmented cells, indicative of retinal pigment epithelial cells. Immunohistochemistry identified cells expressing α-smooth muscle actin, glial fibrillary acidic protein, Bestrophin-1, and F4/80, suggesting the presence of multiple cell types in PVR. Robust PVR primary cultures (C-PVR) were successfully obtained from human membranes, and these cells retained the expression of cell identity markers in culture. C-PVR cultures formed membranes and band-like structures in culture reminiscent of the human condition. MTX significantly reduced the proliferation and band formation of C-PVR, whereas it had no significant effect on cell migration. MTX also induced regulated cell death within C-PVR as assessed by increased expression of caspase-3/7. Conclusions: PVR cells obtained from human membranes can be successfully isolated, cultured, and profiled in vitro. Using these primary cultures, we identified MTX as capable of significantly reducing growth and inducing cell death of PVR cells in vitro.

Purpose To describe a case of remarkable visual recovery after severe open globe injury. Observations We present a case of a 70-year-old man with an open globe injury with no light perception vision before and after primary repair of his ruptured globe and before secondary vitreoretinal surgery to repair a total retinal detachment with a 360° giant retinal tear and retinal incarceration in a posterior scleral wound who proceeded to recover vision to the 20/60 pinhole to 20/50 level. Conclusions and importance Poor presenting acuity is a known risk factor for poor visual outcome after open globe injury. We hypothesize this remarkable visual recovery could be attributable to the presence of a massive choroidal hemorrhage and limited intraocular hemorrhage elsewhere. In rare cases, vision can improve from the no light perception level after secondary vitreoretinal surgery.

Purpose To describe a case of a patient with acute systemic lupus erythematous (SLE) causing choroidal effusions and to report a novel technique for evaluation of the choroidal fluid which sheds light on effusion pathogenesis. Observations A 37 year-old woman was referred for decreased vision, eye pain and shortness of breath. The patient had bilateral angle closure glaucoma from choroidal effusions and bilateral pleural effusions. Work-up revealed new onset acute SLE. A technique for obtaining suprachoroidal fluid is described, and the fluid was analyzed using Light's criteria and found to be exudative in nature. Conclusions and importance There has been speculation as to pathogenesis of choroidal effusions in a variety of conditions, and many authors believe the most likely process to be transudative. The exudative nature of the fluid in our patient suggests that choroidal effusions in acute SLE are likely caused by inflammation, and not secondary to hypoalbuminemia or another transudative process. Similar analyses of suprachoroidal fluid in other disease processes may help elucidate the underlying pathogenesis and may possibly guide treatment.

Purpose The incidence of syphilitic infections continues to rise and represents a major public health concern, particularly in patients co-infected with human immunodeficiency virus (HIV). The infection has a multitude of clinical presentations and is often referred to as the ‘great imitator.’ We present a rare case of an isolated presumed syphilitic optic nerve gumma and characterize it using newer imaging modalities. Observations A 36-year-old HIV-positive man, compliant with treatment, presented with a five day history of decreased vision in the left eye. On examination his visual acuity was 20/30 with mild dyschromatopsia and an inferior altitudinal field defect in the left eye. Funduscopy demonstrated small cup to disc ratios bilaterally and a swollen and hyperemic left optic disc. Following five months of stable vision, the patient's vision in the left eye declined to 20/60, associated with diffuse visual field loss and continued swelling of the left optic disc. Subsequent magnetic resonance imaging with contrast demonstrated enhancement of the left optic nerve, and his serologies were positive for syphilis. Fluorescein angiography and optical coherence tomography were used to better characterize the lesion being most consistent with a syphilitic optic nerve gumma. Conclusions and importance Gummas of the central nervous system are a rare presentation of neurosyphilis and the last reported gumma of the optic nerve was in 1990. Such lesions have not been characterized using newer imaging modalities including optical coherence tomography and fluorescein angiography, both of which may assist in the diagnosis of this rare entity. With the increased prevalence of syphilis and remarkable response to therapy, syphilitic gummas should be considered in at-risk patients presenting with an optic neuropathy.

Purpose To report the case of a 52-year-old man with Purtscher's retinopathy as the presenting manifestation of immune thrombocytopenic purpura (ITP). Observations Treatment with corticosteroids led to the resolution of hematologic findings within 1 week, and normal visual acuity was achieved after 2 months with no additional treatment. Conclusions and importance This is the first reported association between Purtscher's retinopathy and ITP. Complement activation has been implicated in the pathogenesis of both ITP and Purtscher's retinopathy, and we suggest that the patient's systemic process accounted for the retinal findings.