Decreased peri-parafoveal RPE, EZ and ELM intensity: A novel predictive biomarker for hydroxychloroquine retinal toxicity.

PURPOSE: To evaluate the reflectivities of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) in the central fovea, perifoveal, and parafoveal regions with Optical Coherence Tomography (OCT) and the change in choroid vascular index (CVI) in patients using hydroxychloroquine (HCQ). METHODS: Sixty-one patients underwent HCQ treatment; age and sex-matched 44 control group subjects were included in the study. The RPE, EZ, and ELM reflectivities were measured with the ImageJ program at 5 points, and CVI was calculated. RESULTS: RPE, EZ, and ELM reflectivities in the central fovea were higher in the HCQ group than in the control group (p < 0.001, p = 0.013, p = 0.022). In the HCQ group, there was a decrease in RPE reflectivities in the temporal, nasal parafovea, and nasal perifovea (p = 0.001, p = 0.03, p = < 0.001). EZ and ELM reflectivity in the nasal parafovea and nasal perifovea was lower in the patient group than in the control group (p = 0.007, p = 0.005, p = 0.009, p = 0.001). In the HCQ group, all absolute para and perifoveal reflectivities relative to the fovea decreased significantly more than in the control group (p < 0.05). CONCLUSION: In patients who underwent HCQ treatment, there is a decrease in the reflectivities of the para and perifoveal RPE, EZ, and ELM compared to the fovea. This decrease is more pronounced than the decrease in reflectivity in the para and perifoveal regions compared to the fovea in people who do not use HCQ. This situation can be considered as a sign of toxicity that is a precursor to overt maculopathy.

Association of ocular surface and meibomian gland alterations with silicone hydrogel contact lens wear.

PURPOSE: To evaluate silicone hydrogel contact lens (SH-CL) effects on the meibomian glands, corneal structure, and ocular surface parameters. METHODS: Fifty SH-CL wearers for at least 6 months, and 50 sex and age-matched control subjects were recruited for this cross-sectional study. Visual display terminal (VDT) work and CL wear duration were questioned, ocular surface and tear functions were evaluated using OSDI questionnaire, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer test. Corneal sensitivity was measured with Cochet-Bonnet aesthesiometry. Meibography and in vivo confocal microscopy (IVCM) were performed to evaluate meibomian glands and corneal structure. Intergroup comparisons were made using the Chi-square test, Wilcoxon test, or Kruskal-Wallis test. RESULTS: In the CL group, TBUT was shorter (P = 0.01), corneal fluorescein staining (P = 0.04), OSDI scores (P < 0.001), and meiboscores (P < 0.001) were higher than the control group. The biomicroscopic evaluation revealed meibomian gland dysfunction (MGD) in 34 % of the CL group and 20 % of the control group, which was not statistically significant (P > 0.05). IVCM showed that endothelial cell density was lower (P = 0.01) and polymegethism was higher (P < 0.001) in the CL group. Subbasal nerve density and corneal sensitivity measurements were similar in the two groups (P > 0.05). The longer VDT work duration was associated with increased CFS in the CL group (P = 0.05). CONCLUSION: The results showed that SH-CL wear increased dry eye symptoms and ocular discomfort, especially in longer VDT work duration. Meibography revealed significantly worse results in SH-CL wearers. SH-CL-related ocular discomfort seems to be more associated with MGD rather than neurosensorial alterations.

Spontaneous Partial Regression of Bilateral Grade III Corneal Dermoids Associated With Fetal Valproate Spectrum Disorder.

PURPOSE: The purpose of this study was to describe a rare case of a child with bilateral central corneal dermoids (grade III) in association with fetal valproate spectrum disorder (FVSD) and to report the spontaneous regression of these tumors. METHODS: Clinical records of a 14-month-old child whose mother took sodium valproate all along her pregnancy were retrospectively reviewed. The diagnosis of FVSD was made based on phenotypic features and associated congenital malformations. Facial features included trigonocephaly, flat nose bridge and small upturned nose, cleft palate and lip, and micrognathia. Systemic anomalies included bilateral radial defects and club hands, pes equinovarus, hypospadias, secundum atrial septal defect, patent ductus arteriosus, and aortic insufficiency. Cytogenetic studies were normal. RESULTS: Ocular findings included bilateral central corneal dermoids sparing the limbus and peripheral cornea, bilateral aphakia, absence of left anterior chamber, and bilateral mass-like vitreal opacities. A computed tomography scan suggested minimal left microphthalmia. Owing to the high-risk category for general anesthesia and prioritization of other severe systemic anomalies, no ocular surgical intervention was performed. Over 5 years of follow-up, spontaneous partial regression of the corneal tumors was observed. CONCLUSIONS: The development of bilateral grade III corneal dermoids in a child with FVSD may be more than fortuitous and enlarges the list of ocular anomalies associated with FVSD. Corneal dermoids may regress spontaneously.

Ocular Surface, Meibomian Gland Alterations, and In Vivo Confocal Microscopy Characteristics of Corneas in Chronic Cigarette Smokers.

PURPOSE: To evaluate the ocular surface, meibomian gland alterations, and in vivo confocal microscopy (IVCM) parameters through correlation with nicotine dependency level (NDL) and duration of smoking (DS) in chronic smokers. METHODS: This cross-sectional study included 50 eyes of 50 chronic smokers, and 50 eyes of 50 age- and gender-matched healthy nonsmokers. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet esthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index (OSDI) questionnaire were performed consecutively. Basal epithelial cell, keratocyte, and endothelial cell density, the percentage of endothelial polymegethism/pleomorphism, and subbasal nerve plexus were evaluated using IVCM. Meibomian gland density was evaluated with a meibography unit. The Fagerström test was used to measure NDL, and DS was recorded. RESULTS: In the chronic smokers group, the basal epithelial cell density, anterior and posterior keratocytes, endothelial cell density, and long and total subbasal nerve numbers were lower, and LG staining, meiboscore, and OSDI scores were higher, compared with the control group, whereas other parameters were similar. The percentage of polymegethism was higher and the percentage of pleomorphism was lower in the chronic smokers group. In the correlation analysis, no significant relationship was found between the DS, NDL and ocular surface, and IVCM findings. CONCLUSION: Decreased corneal basal epithelium, anterior and posterior keratocytes, endothelial cell density, meibomian gland density, and subbasal nerve numbers were found in chronic smokers. The results of the study show that smoking has an adverse effect on ocular surface parameters.

Sensory Adaptation to Silicone Hydrogel Contact Lens Wear Is Not Associated With Alterations in the Corneal Subbasal Nerve Plexus.

PURPOSE: To evaluate corneal subbasal nerve alterations in contact lens (CL)-naive silicone hydrogel CL wearers and to investigate the relationship between structural subbasal nerve changes with corneal sensitivity. METHODS: Twenty eyes of 20 neophyte daily silicone hydrogel CL wearers and 20 eyes of age-matched control subjects were recruited for this prospective longitudinal study. Corneal subbasal nerve densities were evaluated using in vivo confocal microscopy. Central corneal tactile sensitivity was measured using Cochet-Bonnet esthesiometers. In vivo confocal microscopy and Cochet-Bonnet esthesiometry were performed before and at the 6-month time point after the initiation of CL wear. Two-way repeated measures analysis of variance, χ, and Wilcoxon signed-rank tests were used for statistical analyses. RESULTS: The mean ages of CL users and control subjects were 21.8 ± 1.8 years (range = 19-24 years) and 21.5 ± 2.3 years (range = 20-24 years), respectively (P = 0.579). Compared with their baseline values, there were no significant changes at the 6-month follow-up period in the mean total subbasal nerve fiber length (2266.6 ± 414.6 vs. 2277.9 ± 405.0 µm/frame; P = 0.432), mean total subbasal nerve branch density (10.4 ± 1.5 vs. 10.5 ± 1.3 nerves/frame; P = 0.655), or the mean long nerve fiber density (4.7 ± 0.7 vs. 4.8 ± 0.7 nerves/frame; P = 0.564) of CL users. Mechanical corneal sensitivity remained unaltered during the 6-month period in CL users (11.2 ± 0.5 vs. 11.2 ± 0.5; P = 1.000). No significant changes were observed in the subbasal nerve plexus or corneal tactile sensitivity of the control subjects during the study interval. CONCLUSIONS: Sensory adaptation to CL wear is not mediated through attenuation of the subbasal nerve or reduction of corneal tactile sensitivity in CL-naive users.

Polysorbate 20 increases oral absorption of digoxin in wild-type Sprague Dawley rats, but not in mdr1a(-/-) Sprague Dawley rats.

The aim was to investigate the ability of polysorbate 20 to alter oral digoxin absorption in vitro and drug exposure in vivo via modulation of transporter mediated efflux. Transport studies were performed in MDCKII-MDR1 and Caco-2 cells using 3H-digoxin. Pharmacokinetic studies were performed in wild type and mdr1a deficient Sprague Dawley rats. 3H-digoxin was quantified using liquid scintillation counting. The results showed an increased absorptive transport and a reduced secretory transport in MDCKII-MDR and Caco-2 cells as a function of polysorbate 20 concentrations. The secretory transport (B-A) of digoxin was reduced by 50% at lower polysorbate 20 concentrations than required to increase the absorptive transport (A-B). In vivo, the oral bioavailability of digoxin in wild type animal was increased by 10-25% (w/v) polysorbate 20. In mdr1a deficient Sprague Dawley rats 25% (w/v) polysorbate 20 did not alter the absorption of digoxin after oral administration, but digoxin exposure was significantly different between wild type and mdr1a deficient rats. In conclusion, polysorbate 20 increased absorptive transport across Caco-2 cell monolayers and in vivo in rats in a concentration dependent manner, most likely via inhibition of P-gp rather than through solubilization of digoxin.