Changes in choroidal structure following intravitreal aflibercept therapy for retinal vein occlusion

Aims To examine the choroidal change accompanying retinal vein occlusion (RVO) in detail, we measured changes in choroidal structure after intravitreal aflibercept (IVA) injections for RVO using binarisation of enhanced depth imaging optical coherence tomographic (EDI-OCT) images and assessed associations with clinical outcome. Methods Retrospective, observational case series. Forty treatment-naïve patients (10 central, 18 major branch and 12 macular branch RVO) were examined by EDI-OCT before and 1, 3 and 6 months after IVA injections. EDI-OCT images were binarised using ImageJ. Subfoveal cross-sectional areas of the luminal, stromal and total choroid over a 1500 µm span were measured and the stromal area to total choroidal area (S/C) ratio was calculated. Results Compared to normal contralateral eyes, afflicted eyes at baseline exhibited significantly greater stromal area (p<0.001), total choroidal area (p=0.001) and S/C ratio (p<0.001), but no difference in luminal area (p=0.083). The stromal area, S/C ratio and total choroidal area were significantly reduced in afflicted eyes at 1, 3 and 6 months after IVA (all p<0.006). Baseline S/C ratio was significantly correlated with baseline visual acuity (VA), baseline central retinal thickness (CRT) and VA and CRT improvement at 1, 3 and 6 months post-treatment even after adjusting for the axial length, age and sex (all p<0.012). Conclusion RVO induces substantial oedema of the choroidal stromal area that is detectable by binarisation of EDI-OCT images. This stromal oedema likely stems from high intraocular vascular endothelial growth factor levels. Changes in choroidal structure may be used to assess severity and prognosis of RVO

Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren’s Syndrome

Background: Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren’s syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. 　 　Methods and Finding: Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. 　Conclusion: Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces

Anti-inflammatory effects of rebamipide eyedrop administration on ocular lesions in a murine model of primary Sjögren's syndrome.

Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown.Reb eyedrops were administered to the murine model of SS aged 4-8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment.Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces

Lactoferrin in tears from Reb-treated mice and direct effect of Reb on lacrimal glands.

<p>(A) The lactoferrin concentrations in the tears from Reb-treated mice were determined using ELISA. Results are expressed as mean ± SD for five mice per group. (B) Lacrimal gland cells from Tx-NFS/<i>sld</i> mice were cultured with or without Reb (0.25 mM) for 6 h, and the lactoferrin mRNA levels in cultured Lg fragments were then analyzed using real-time RT-PCR. Results are expressed as mean ± SD of triplicate determinations per group from 3 independent experiments. *<i>P</i><0.05, **<i>P</i><0.01.</p

Lactoferrin in tears from Reb-treated mice and direct effect of Reb on lacrimal glands.

<p>(A) The lactoferrin concentrations in the tears from Reb-treated mice were determined using ELISA. Results are expressed as mean ± SD for five mice per group. (B) Lacrimal gland cells from Tx-NFS/<i>sld</i> mice were cultured with or without Reb (0.25 mM) for 6 h, and the lactoferrin mRNA levels in cultured Lg fragments were then analyzed using real-time RT-PCR. Results are expressed as mean ± SD of triplicate determinations per group from 3 independent experiments. *<i>P</i><0.05, **<i>P</i><0.01.</p

Therapeutic effects of Reb eyedrop administration on tear secretion in the murine model of SS.

<p>Average tear volumes after pilocarpine administration (2.5 mg/kg) were measured for 5 min (0–5 min and 5–10 min). Results are expressed as means ± SD for 5 mice per group. Control, nonthymectomized (non-Tx) NFS/<i>sld</i> mice. ** <i>P</i><0.005<b>.</b></p

Anti-inflammatory proteins in the ocular lesions in Reb-treated murine model of SS.

<p>The mRNA expression levels of TGF-β (A), IL-10 (B), and mucin 5AC (C) in conjunctival tissues in Reb-treated (0% and 1%) mice were analyzed using real-time RT-PCR. Results expressed as mean ± SD for five mice per group.</p

Effect of Reb eyedrops on the ocular lesions in the murine model of SS.

<p>(A) Ocular surface lesions in Reb-treated mice were examined using fluorescein staining of the ocular surface. Representative photomicrographs for each group are shown. (B) The scores for corneal epithelial disorders. Results are expressed as mean ± SD for five mice per group. *<i>P</i><0.05, **<i>P</i><0.005.</p