Ocular manifestations of systemic isotretinoin in patients with acne: a systemic review and meta-analysis.

PURPOSE: To examine the effects of systemic isotretinoin treatment on the eye using several ocular examination parameters. METHODS: We conducted a systemic review for literature published up to June 2021 in both PubMed and Web of Science databases. We included prospective observational or interventional studies evaluating ocular manifestations of isotretinoin in acne patients. The primary outcome measures were anaesthetized and non-anaesthetized Schirmer test, tear break-up time (TBUT), central corneal thickness (CCT), average retinal nerve fibre layer (RNFL) thickness, ganglion cell-inner plexiform layer (GC-IP) thickness, subfoveal choroidal thickness, axial length, ocular surface disease index (OSDI), meibomian gland expression (MGE) and conjunctival stain. The National Institute of Health (NIH) quality assessment tools were used to assess the data quality. The effect size used to analyse the included studies was the weighted mean difference (WMD) and its related confidence intervals (95%CIs). RESULTS: Twenty-one publications involving 1105 eyes of 842 participants met the inclusion criteria. Isotretinoin use was significantly associated with reduction in the scores of anaesthetized Schirmer (WMD = -2.23, 95%CI: -3.28 to -1.18), non-anaesthetized Schirmer (WMD = -3.74, 95%CI: -4.23 to -3.25), TBUT (WMD = -3.47, 95%CI: -5.09 to -1.86), and CCT (WMD= -7.39, 95%CI: -13.91 to -0.88). Isotretinoin use was significantly associated with increase of OSDI (WMD = 18.29, 95%CI: 7.54-29.03), MGE (WMD = 1.02, 95%CI: 0.70-1.33) and conjunctival stain scores (WMD = 0.61, 95%CI: 0.47-0.76). No significant change was noted in RNFL thickness (WMD = -0.64, 95%CI: -1.80 to 0.51); GC-IP thickness (WMD = 0.42, 95%CI: -1.08 to 1.92); subfoveal choroidal thickness (WMD = -1.80, 95%CI: -6.69 to 3.09), and axial length (WMD = 0.08, 95%CI: -0.19 to 0.35). A significant heterogeneity was found between the study estimates in each of anaesthetized Schirmer, TBUT, MGE, OSDI, and conjunctival stain tests. CONCLUSION: Isotretinoin use results in a statistically significant reduction of the central corneal thickness, TBUT, and Schirmer test scores. A statistically significant increase in MGE, OSDI and conjunctival stain scores was found. No statistically significant change of average RNFL, GC-IP thickness, subfoveal choroidal thickness, or axial length was observed. Further well-designed studies should evaluate the long-term effect of isotretinoin on the eye and reach a firmer conclusion.

MEK2 is a critical modulating mechanism to down-regulate GCIP stability and function in cancer cells.

Loss of tumor suppressor activity and upregulation of oncogenic pathways simultaneously contribute to tumorigenesis. Expression of the tumor suppressor, GCIP (Grap2- and cyclin D1-interacting protein), is usually reduced or lost in advanced cancers, as seen in both mouse tumor models and human cancer patients. However, no previous study has examined how cancer cells down-regulate GCIP expression. In this study, we first validate the tumor suppressive function of GCIP using clinical gastric cancer tissues and online database analysis. We then reveal a novel mechanism whereby MEK2 directly interacts with and phosphorylates GCIP at its Ser313 and Ser356 residues to promote the turnover of GCIP by ubiquitin-mediated proteasomal degradation. We also reveal that decreased GCIP stability enhances cell proliferation and promotes cancer cell migration and invasion. Taken together, these findings provide a more comprehensive view of GCIP in tumorigenesis and suggest that the oncogenic MEK/ERK signaling pathway negatively regulates the protein level of GCIP to promote cell proliferation and migration.

Visual deficits and cognitive assessment of multiple sclerosis: confounder, correlate, or both?

BACKGROUND: The relationship between visual impairment and cognitive performance in multiple sclerosis (MS) remains poorly understood. OBJECTIVE: To determine associations between visual acuity and optical coherence tomography (OCT) measures with cognitive performance of MS patients and healthy controls (HCs). METHODS: 141 MS patients (with and without MS optic neuritis; MSON) and 50 HCs underwent neuropsychological, visual, and OCT testing. California Verbal Learning Test (CVLT-II), Brief Visuospatial Memory Test (BVMT-R), and Symbol Digit Modalities Test (SDMT) were used. Patients with test performance below - 1.5 standard deviations of the mean HCs scores were labeled as cognitive impairment. Visual ability was assessed with 100%, 2.5%, and 1.25% low-contrast letter acuity (LCLA) charts. OCT-derived peripapillary retinal nerve fiber layer (pRNFL) thickness, macular volume (MV), macular ganglion cell inner plexiform (mGCIP) thickness (as a sum of GC and IP layers), and macular inner nuclear layer (mINL) were computed. RESULTS: 100% and 2.5% LCLA associated with SDMT in MS and HCs (p < 0.001; and p < 0.012, respectively). In MSON patients, visually demanding tests were explained by pRNFL and macular volume for SDMT (ß = 0.172, p = 0.039 and ß = 0.27, p = 0.001) and MV for BVMT-R (ß = 0.21, p = 0.012). In non-MSON, only mINL was predictor of CVLT-II. pRNFL and MV predicted cognitive impairment with an accuracy of 72.2% (Negelkerke R2 = 0.234). These findings were driven by associations within the progressive MS subgroup. HC's SDMT performance was explained by mGCIP (ß = 0.316, p = 0.001). CONCLUSIONS: Both LCLA and OCT-based measures (pRNFL and macular volume) were associated with MS cognitive performance. OCT-based measures were also significant predictors of cognitive status in MS patients. mGCIP associated with cognitive performance in HCs.

Correlation of neutrophyle/lymphocyte ratio and pulmonary parameters with optic coherence tomography findings in stable chronic obstructive pulmonary disease.

INTRODUCTION: To examine the correlation of pulmonary functions and neutrophyle/lymphocyte ratio (NLR) with optic coherence tomography findings in stable chronic obstructive pulmonary disease (COPD). METHODS: Fifty-five COPD (110 eyes) and 48 control cases (96 eyes) were enrolled. COPD patients were grouped as Group 1 (mild-moderate) and Group 2 (severe) according to GOLD classification. Subfoveal choroidal thickness (SFCT), ganglion cell-inner plexiform layer (GCIP) and retinal nerve fiber layer (RNFL) analysis by SD-OCT were performed in follow up. NLR was calculated by blood cell count. RESULTS: Inferior RNFL and average GCIP of COPD were lower than control during the initial and sixth month examination (P = .002, P < .001, respectively). Average RNFL and SFCT were lower in COPD patients in sixth month examination (P = .020, P = .015, respectively). Average, temporal, inferior, nasal RNFL and SFCT in sixth month examination were significantly lower in severe COPD (P < .05 for all), but average GCIP were similar (P = .015). Disease duration, Modified Medical Research Council (mMRC) and attacks/year showed significant negative correlations, whereas forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) showed significant positive correlations with OCT values. NLR was significantly higher in COPD cases compared to control (P < .001) and had a negative correlation with GCIP values. CONCLUSION: Chronic obstructive pulmonary disease severity is shown to have a negative effect on OCT measurements. SD-OCT can reflect severity of inflammation, and suggested to be used in follow up of COPD cases. NLR may have a role to predict the ganglion cell damage in COPD patients.