Assessment of tilt and decentration of crystalline lens and intraocular lens relative to the corneal topographic axis using anterior segment optical coherence tomography

<div><p>Purpose</p><p>To investigate the tilt and decentration of the crystalline lens and the intraocular lens (IOL) relative to the corneal topographic axis using anterior segment ocular coherence tomography (AS-OCT).</p><p>Methods</p><p>A sample set of 100 eyes from 49 subjects (41 eyes with crystalline lenses and 59 eyes with IOLs) were imaged using second generation AS-OCT (CASIA2, TOMEY) in June and July 2016 at Okayama University. Both mydriatic and non-mydriatic images were obtained, and the tilt and decentration of the crystalline lens and the IOL were quantified. The effects of pupil dilation on measurements were also assessed.</p><p>Results</p><p>The crystalline lens showed an average tilt of 5.15° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 5.25° under mydriatic conditions. Additionally, an average decentration of 0.11 mm towards the temporal direction was observed under non-mydriatic conditions and 0.08 mm under mydriatic conditions. The average tilt for the IOL was 4.31° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 4.65° in the same direction under mydriatic conditions. The average decentration was 0.05 mm towards the temporal direction under non-mydriatic conditions and 0.08 mm in the same direction under mydriatic conditions. A strong correlation was found between the average tilt and decentration values of the crystalline lens and the IOL under both non-mydriatic and mydriatic conditions (all Spearman correlation coefficients, r ≥ 0.800; all P < 0.001).</p><p>Conclusion</p><p>When measured using second generation AS-OCT, both the crystalline lens and the IOL showed an average tilt of 4–6° toward the inferotemporal direction relative to the corneal topographic axis and an average decentration of less than 0.12 mm towards the temporal direction. These results were not influenced by pupil dilation and they showed good repeatability.</p></div

AICAR suppressed tumor angiogenesis and inflammatory cells infiltration.

<p>(A, B) Microvessel density in tumor tissues was determined by immunofluorescent staining by an endothelial-specific antibody CD31. (A) Control group and (B) AICAR-treated group. (C) Quantitative analysis of fluorescent-positive area (per 4000 µm²) in tumors. Vessel density was significantly suppressed in AICAR-treated mice group (**p<0.01). (D, E) Macrophage- and neutrophil- infiltration in Y79 xenografts. Typical photomicrographs of immunofluorescent staining for CD11b (red) in Y79 xenografts. Nuclei were stained with propidium iodide (blue). Y79 cells isolated from control mice (D) and AICAR-treated mice (E). (F) Quantitative analysis of the CD11b (+) cells/DAPI (+) cells ratio in tumors. The number of CD11b (+) cells was significantly lower in the AICAR-treated mice group than in the control mice group (**p<0.01). Each column represents the mean ± SEM. Scale bars (A, B, D, E), 200 µm.</p

Intraclass correlation coefficients calculated between pre- and postoperative decentration data from the crystalline lens and the intraocular lens.

<p>Intraclass correlation coefficients calculated between pre- and postoperative decentration data from the crystalline lens and the intraocular lens.</p

Intraclass correlation coefficients calculated between pre- and postoperative tilt data from the crystalline lens and the intraocular lens.

<p>Intraclass correlation coefficients calculated between pre- and postoperative tilt data from the crystalline lens and the intraocular lens.</p

General characteristics of the patient group.

<p>General characteristics of the patient group.</p

AICAR suppressed proliferation and induced apoptosis of retinoblastoma in vivo.

<p>(A, B) Immunofluorescent analysis for Ki67 of tumors of Y79 cells isolated from control mice (A) and AICAR-treated mice (B). Nuclei were stained with propidium iodide (red). (C) Quantitative analysis of Ki67 (+) cells/PI (+) cells ratio in tumors. Values are significantly lower in the AICAR-treated mice group than in the control mice group (**p<0.01). (D,E) Apoptotic cells in retinoblastoma xenografts. Typical photomicrographs of apoptotic cells using TUNEL assay (green) in Y79 xenografts. Nuclei were stained with propidium iodide (red). Y79 cells isolated from control mice (D) and AICAR-treated mice (E). (F) Quantitative analysis of the apoptotic cell percentage in tumors. Note that the number of TUNEL (+) cells was significantly higher in the AICAR-treated mice group than in the control mice group (**p<0.01). Each column represents the mean ± SEM. Scale bars (A, B, D, E), 200 µm.</p

Mean tilt and decentration of the crystalline lens and the IOL.

<p>Mean tilt and decentration of the crystalline lens and the IOL.</p

Proposed mechanism of action for AICAR in human retinoblastoma in an in-vivo xenograft model.

<p>AICAR administration leads to activation of AMPK decreased tumor vessel density and decreased CD11b (macrophage) infiltration. Activated AMPK inhibits mTOR pathway, protein synthesis and cell growth. In addition, AICAR administration results in decreased levels of p21, which was recently found to inhibit apoptosis and promote cell proliferation. Overall signaling changes leads to loss of viability due to apoptosis, proliferation block and inhibition of tumor progression.</p

AICAR does not alter the levels of cyclins A, D and E in retinoblastoma in vivo.

<p>Quantitative RT-PCR analysis of tumors treated with AICAR in comparison with control shows no significant difference. Each column represents the mean ± SEM.</p

Postoperative complications.

<p>Postoperative complications.</p