Neurotrophic keratitis in a patient with disseminated lymphangiomatosis.

INTRODUCTION: Neurotrophic keratitis, a degenerative corneal disease caused by trigeminal nerve impairment, has many etiologies and remains very difficult to treat. METHODS: Case report of a 23-year-old male with a right corneal ulcer that failed to improve despite broad-spectrum antimicrobials. RESULTS: Prior diagnosis of disseminated lymphangiomatosis with a lesion in the right petrous apex effacing Meckel's (trigeminal) cave in conjunction with a history of nonhealing corneal abrasions suggested a neurotrophic etiology. Drawstring temporary tarsorrhaphy, in addition to antibiotics and autologous serum, lead to successful clearing of the infection and resolution of the corneal ulcer. Visual acuity improved from light perception (LP) at the peak of infection to 20/40 six weeks after treatment. CONCLUSIONS: To our knowledge, we report the first case of neurotrophic keratitis in a patient with disseminated lymphangiomatosis that caused a mass effect in Meckel's (trigeminal) cave leading to compression of the trigeminal nerve. The antibiotic-resistant corneal ulcer was successfully treated with drawstring tarsorrhaphy, confirming the utility of this therapeutic measure in treating neurotrophic keratitis

High-Risk Corneal Graft Rejection in the Setting of Previous Corneal Herpes Simplex Virus (HSV)-1 Infection

Acknowledgments The authors thank M. Robertson and R. Fordyce for technical support during the duration of the study. The work performed in Aberdeen was supported by grant from Action Medical Research UK (SP4328; London, England, UK), NHS Grampian Endowment grant (12/49; Aberdeen, Scotland, UK), and Saving Sight in Grampian (Charity No.SC002938; Aberdeen, Scotland, UK). The work performed in Pittsburgh was supported by a Fight for Sight Post-Doctoral Award (JEK; New York, NY, USA); unrestricted grants from the Western Pennsylvania Medical Eye Bank Foundation (Pittsburgh, PA, USA), Research to Prevent Blindness (New York, NY, USA), and the Eye and Ear Foundation of Pittsburgh (RLH; Pittsburgh, PA, USA); and National Institutes of Health Grants P30EY08098 (RLH; Bethesda, MD, USA) and EY10359 (RLH).Peer reviewedPublisher PD

Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia

Background\ud Therapeutic vaccines can be designed to enhance existing T cell memory populations for increased protection against re-infection. In the case of herpes simplex virus type 1, recurrent disease results from reactivation of latent virus in sensory ganglia, which is controlled in part by a ganglia-resident HSV-specific memory CD8+ T cell population. Thus, an important goal of a therapeutic HSV-1 vaccine would be to enhance this population.\ud \ud Methods\ud HSV-1-infected mice were treated with TAK-779 to block CCR5- and CXCR3-mediated CD8+ T cell migration during both acute and latent infections. Additionally, HSV-1-specific CD8+ T cells were transferred into HSV-1 latently infected mice to mimic the effect of a therapeutic vaccine, and their migration into trigeminal ganglia (TG) was traced during steady-state latency, or during recovery of the TG-resident memory CD8+ T cell population following stress-, and corticosterone-induced depletion and HSV-1 reactivation from latency. Bromodeoxy uridine (BrdU) incorporation measured cell proliferation in vivo.\ud \ud Results\ud TAK-779 treatment during acute HSV-1 infection reduced the number of infiltrating CD8+ T cells but did not alter the number of viral genome copies. TAK-779 treatment during HSV latency did not affect the size of the TG-resident memory CD8+ T cell population. Transferred HSV-specific CD8+ T cells failed to access latently infected TG during steady-state latency, or during recovery of the TG resident HSV-specific CD8+ T cell population following exposure of latently infected mice to stress and corticosterone. Recovery of the HSV-specific CD8+ T cell population after stress and corticosterone treatment occurred with homeostatic levels of cell division and did not require CD4+ T cell help.\ud \ud Conclusions\ud Our findings are consistent with the notion that the CD8+ T cells in latently infected TG are a tissue-resident memory (Trm) population that is maintained without replenishment from the periphery, and that when this population is disrupted, it recovers without proliferation or detectable recruitment of HSV-specific CD8+ T cells from the blood. The compartmentalization of the HSV-specific CD8+ memory T cell population in latently infected TG will complicate the design of therapeutic vaccines

Stratification of Antigen-presenting Cells within the Normal Cornea

The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD11c promoter (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c+ dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 µm in length and traverse up 20 µm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c-CD11b+ putative macrophages that express low levels of MHC class II. Finally, MHC class IIpCD11c-CD11b+ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma

Elevated CD1c(+) Myeloid Dendritic Cell Proportions Associate With Clinical Activity and Predict Disease Reactivation in Noninfectious Uveitis

PURPOSE. To test the association between elevated proportions of CD1c(+) myeloid dendritic cells (mDCs) and disease activation/reactivation in noninfectious uveitis. METHODS. Noninfectious uveitis patients (n = 89) and healthy controls (n = 111) were recruited. The proportion of CD1c(+) mDCs in the total dendritic cell (DC) population of peripheral blood was measured by flow cytometry (CD1c(+) mDCs gated on Lineage 1(+)HLADR(+) DCs). Disease activity was assessed per Standardization of Uveitis Nomenclature criteria. Uveitis reactivation was ascribed to clinically quiescent patients who developed reactivation of intraocular inflammation within 6 months. RESULTS. The proportions of CD1c(+) mDCs were increased in noninfectious uveitis patients, especially in active disease, compared to healthy controls. This CD1c(+) mDC elevation was not associated with underlying systemic diseases, anatomic locations of uveitis, medications, or demographic factors. Longitudinal data showed that the dynamics of CD1c(+) mDC levels were correlated with disease activity. The average proportion of CD1c(+) mDCs in active uveitis patients was 60% so we set this as the cutoff between high and low CD1c(+) mDC levels. Although 74% of quiescent patients had low proportions of CD1c(+) mDCs, 26% still had high proportions. Quiescent patients with high CD1c(+) mDC proportions showed increased risk of disease reactivation, compared to quiescent patients with low CD1c(+) mDC proportions. CONCLUSIONS. Increased proportions of CD1c(+) mDCs were associated with clinical activity, and quiescent patients with elevated CD1c(+) mDCs were more likely to undergo reactivation. This suggests that CD1c(+) mDC proportion may be a potential biomarker for assessing clinical activation and reactivation in noninfectious uveitis.National Institutes of Health (NIH)/National Eye Institute (NEI) NIH Medical Research Scholars Program Pan-American Ophthalmological Foundation/Retina Research Foundation CONICY

Immunology and Microbiology Elevated CD1c þ Myeloid Dendritic Cell Proportions Associate With Clinical Activity and Predict Disease Reactivation in Noninfectious Uveitis

Citation: Chen P, Urzua CA, Knickelbein JE, et al. Elevated CD1c þ myeloid dendritic cell proportions associate with clinical activity and predict disease reactivation in noninfectious uveitis