Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response

Cruzat, Andrea; Schrems, W.; Schrems-Hoesl, Laura M.; Cavalcanti, Bernardo M.; Baniasadi, Neda; Witkin, Deborah; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram

doi:10.1167/iovs.15-16560

Cited by 61 publications

(52 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…28,29 However, no significant difference was noted between our two groups after adjusting for clinical parameters including DED severity. Steger and associates 25 also have observed a significantly lower number of subbasal nerves per frame in the GVHD group than in a control group without GVHD.…”

Section: Discussionmentioning

confidence: 64%

In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease

Kheirkhah

Qazi

Arnoldner

et al. 2016

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Citation: Kheirkhah A, Qazi Y, Arnoldner MA, Suri K, Dana R. In vivo confocal microscopy in dry eye disease associated with chronic graftversus-host disease. Invest Ophthalmol Vis Sci. 2016;57:4686-4691. DOI:10.1167/iovs.16-20013 PURPOSE. To compare densities of corneal epithelial dendritic cells (DCs), corneal subbasal nerves, and conjunctival epithelial immune cells (EICs) between patients with dry eye disease (DED) with and without graft-versus-host disease (GVHD) using in vivo confocal microscopy (IVCM).METHODS. This study included 54 patients who had moderate to severe DED either associated with (n ¼ 33) or without (n ¼ 21) chronic GVHD. In addition to evaluating clinical parameters of DED, images obtained by laser-scanning IVCM of the central cornea and superior tarsal conjunctiva were analyzed to measure densities of corneal epithelial DCs, corneal subbasal nerves, and conjunctival EICs. RESULTS.Although there were no significant differences between GVHD and non-GVHD groups in symptom scores, the GVHD group had significantly worse corneal fluorescein staining, tear break-up time, and Schirmer's scores than the non-GVHD group. Corneal epithelial DC density, corneal subbasal nerve density, and conjunctival EIC density were 148 6 135 cells/mm 2 , 16.3 6 6.1 mm/mm 2 , and 670 6 267 cells/mm 2 , respectively, in the GVHD group; and 122 6 99 cells/mm 2 , 18.3 6 5.1 mm/mm 2 , and 572 6 271 cells/mm 2 , respectively, in the non-GVHD group. After adjusting for clinical parameters, including the DED severity, none of the IVCM parameters was significantly different between the GVHD versus non-GVHD groups (P ¼ 0.82, P ¼ 0.21, and P ¼ 0.60, respectively).CONCLUSIONS. In GVHD-associated DED, cellular changes in the cornea and conjunctiva observed by IVCM were similar to those seen in patients who have non-GVHD dry eye with the same level of disease severity. Therefore, corneal and conjunctival IVCM findings in GVHD-associated DED are possibly reflective of the local disease (DED) severity rather than the underlying systemic disease process.

show abstract

Section: Discussionmentioning

confidence: 64%

In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease

Kheirkhah

Qazi

Arnoldner

et al. 2016

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the molecular basis of corneal sensitivity remains unclear, previous reports have described the bilateral responses in the patients with unilateral diseases or peripheral unilateral nerve lesions, including the infectious keratitis, which may be related to the sympathetic reaction caused by the central nervous system. 19,[35][36][37] Considering that intravitreal-injected bevacizumab could be detected in the cornea, 38 multiple intravitreal injections of bevacizumab may cause impairment of corneal innervations and epithelial functions, which needs to be evaluated in the future.…”

Section: Discussionmentioning

confidence: 99%

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Dong

Zhang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Dong M, Di G, Zhang X, Zhou Q, Shi W. Subconjunctival bevacizumab injection impairs corneal innervations and epithelial wound healing in mice. Invest Ophthalmol Vis Sci. 2017;58:146958: -147758: . DOI: 10.1167 PURPOSE. To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice.METHODS. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-b3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF.RESULTS. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection.CONCLUSIONS. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea.

show abstract

“…202 More recent prospective studies demonstrated that the decrease in subbasal corneal nerve density is associated with increased density and morphological changes of central epithelial dendritic cells in patients with infectious keratitis, including bacterial, fungal and Acanthamoeba keratitis, suggesting a potential direct interaction between the immune and nervous system in the cornea (Figure 7). 88,203 Kobayashi et al studied patients with cytomegalovirus corneal endotheliitis by IVCM and also found reduced subbasal nerves. 204 Recently, our group showed that patients with infectious keratitis who sustain profound loss of corneal nerves during the acute phase of infection experienced corneal nerve regeneration of subbasal nerves during the first 6 months after the resolution of infection.…”

Section: Correlation Of Corneal Nerve Alterations To Corneal Sensmentioning

confidence: 99%

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

2017

Self Cite

View full text Add to dashboard Cite

In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to that of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, and proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.

show abstract

Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response

Cited by 61 publications

References 40 publications

In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease

In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

Contact Info

Product

Resources

About