Fingerprint sign of the Henle fibre layer in epiretinal membrane: a cross-sectional and longitudinal study.

PURPOSE: To investigate the incidence and distribution of fingerprint-like microwaves in the Henle fibre layer (HFL) of the eyes with epiretinal membrane (ERM). METHODS: Patients with idiopathic ERM were included. The fingerprint sign was defined using en-face optical coherence tomography images of the HFL, and its extent was classified into three grades. RESULTS: At baseline, fingerprint sign was found in 70 of 83 (84.3%) eyes with ERM and was more frequently observed in eyes with a higher ERM stage (P < 0.001). Its extent increased (P < 0.001) with an increase in ERM stage or the central macular thickness (P < 0.001). Best corrected visual acuity (BCVA) was worse in eyes with a fingerprint sign than in those without (P = 0.024). Metamorphopsia was more common in eyes with a greater extent of fingerprint-like microwaves (P = 0.048). The fingerprint sign persisted over a mean follow-up period of 18.0 ± 23.3 without surgery. In 45 eyes that underwent surgery, the extent of fingerprint-like microwaves decreased at 1.2 months (P = 0.001), and further decreased at 13.7 months postoperatively (P = 0.019). However, the proportion of eyes with a fingerprint sign after surgery was similar to that observed preoperatively (P = 0.912). CONCLUSIONS: Fingerprint-like microwaves were commonly found in eyes with ERM and were associated with ERM severity and BCVA. The microwaves remained long after surgery, although their extent may have decreased after the ERM was resolved. These results suggest that ERM traction may cause long-lasting changes in the HFL.

Quantification of choroidal hyperreflective layer: A swept-source optical coherence tomography study.

PURPOSE: To investigate variation in reflectivity of choroidal layers in normal eyes. METHODS: From the swept-source optical coherence tomography database, we retrospectively included eyes with a normal fundus. Choroidal reflectivity was measured on the horizontal and vertical B-scan optical coherence tomography images. The optical barrier of the choroid was defined as the first hill in the middle of the reflectance graph from the retinal pigment epithelium-Bruch's membrane complex to the chorioscleral junction. RESULTS: The optical barrier of the choroid was identified in 91 eyes of 91 individuals. The amplitude of peak reflectivity of the optical barrier of the choroid at macular center (142.85 ± 15.04) was greater than those in superior (136.12 ± 14.08) or inferior macula (135.30 ± 16.13) (P = 0.028, P = 0.008, respectively). Latency between the peak of the retinal pigment epithelium-Bruch's membrane complex and the optical barrier of the choroid at macular center (48.11 ± 13.78 µm) was shorter than those in nasal macula (55.58 ± 19.21 µm) (P = 0.021). The amplitude of the peak reflectivity of the optical barrier of the choroid in the center negatively correlated with the latency between the retinal pigment epithelium-Bruch's membrane complex and the optical barrier of the choroid (P < 0.001). CONCLUSION: An optical barrier exists in the inner choroid of the normal eye. Its depth depends on the location within the macula. Further studies are mandatory to evaluate variations in the barrier in the eyes with chorioretinal disease.

Bidirectional Dimples After Internal Limiting Membrane Peeling for a Macular Hole.

Purpose: To investigate microstructural changes and prognosis associated with retinal surface dimples after internal limiting membrane (ILM) peeling for macular holes (MHs). Methods: We analyzed swept-source optical coherence tomography (SS-OCT) images of patients who underwent surgery for idiopathic MHs. The inner retinal dimples on SS-OCT images were classified into three types: unidirectional, bidirectional, and complicated bidirectional dimples. Results: Dimples were found in 97.1% of the 69 eyes (69 patients) during a mean follow-up period of 14.0 ± 11.9 months after MH surgery. Of the eyes with dimples, 83.6% had bidirectional dimples. The proportion of eyes with dimples increased from 55.3% at 1 month postsurgery to 95.5% at 3 months and 97.9% at 6 months postsurgery. However, the proportion of eyes with complicated bidirectional dimples gradually increased from 1 month (29.8%) to 3 months (46.3%) and 6 months (64.6%) postsurgery. In the multivariable generalized estimating equation model, complicated bidirectional dimples occurred more frequently in eyes with shorter axial length (P = 0.039) and longer follow-up duration (≥6 months; at 6 months: P = 0.001; at 12 months: P = 0.009). Conclusions: Changes in retinal layers associated with retinal surface dimples after ILM peeling can occur at different retinal depths and over different time courses. These findings suggest the progression of dimple-associated remodeling of the underlying retinal layer. Translational Relevance: Various types of dimples can be used as surrogates to evaluate structural changes and outcomes of MH surgery.

Correlation Between Hyperreflective Foci in the Choroid and Choroidal Discoloration in Vogt-Koyanagi-Harada Disease.

Purpose: To investigate the distribution of hyperreflective choroidal foci (HCF) in eyes with Vogt-Koyanagi-Harada (VKH) disease. Methods: We included 22 eyes of 11 patients with VKH disease in the convalescent stages and 22 eyes of age- and sex-matched normal controls. HCF were quantified using en face optical coherence tomography (OCT) images of the choroid, and the degree of fundus pigmentation was determined by the color balance of the fundus photographs. The results were then analyzed between the eyes with and without sunset glow fundus (SGF). Results: The median age of patients with VKH disease was 58.0 (range 54.0-65.0) years, and median disease duration was 66.4 (range 8.5-147.7) months. In 22 eyes with VKH, the number and total area of HCF were correlated with the degree of fundus pigmentation (ρ = -0.671, P < 0.001; ρ = -0.612, P = 0.002, respectively). The number of HCF was significantly smaller in VKH disease-affected eyes with SGF (median, interquartile range; 134.6, 110.0-159.2) than in those without SGF (229.0, 197.0-261.0) and the eyes of normal controls (211.8, 190.3-233.4). Conclusions: HCF distributions correlated with the degree of fundus pigmentation in eyes with VKH disease. Quantitative measurements of HCF on en face OCT images can be a novel tool in evaluating choroidal pigmentation in patients with VKH disease.

Evaluation of the effect of filtered ultrafine particulate matter on bleomycin-induced lung fibrosis in a rat model using computed tomography, histopathologic analysis, and RNA sequencing.

We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing.

MTF1 Is Essential for the Expression of MT1B, MT1F, MT1G, and MT1H Induced by PHMG, but Not CMIT, in the Human Pulmonary Alveolar Epithelial Cells.

The inhalation of humidifier disinfectants (HDs) is linked to HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) is significantly involved in HDLI, but the correlation between chloromethylisothiazolinone (CMIT) and HDLI remains ambiguous. Additionally, the differences in the molecular responses to PHMG and CMIT are poorly understood. In this study, RNA sequencing (RNA-seq) data showed that the expression levels of metallothionein-1 (MT1) isoforms, including MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X, were increased in human pulmonary alveolar epithelial cells (HPAEpiCs) that were treated with PHMG but not in those treated with CMIT. Moreover, upregulation of MT1B, MT1F, MT1G, and MT1H was observed only in PHMG-treated HPAEpiCs. The protein expression level of metal regulatory transcription factor 1 (MTF1), which binds to the promoters of MT1 isoforms, was increased in PHMG-treated HPAEpiCs but not in CMIT-treated HPAEpiCs. However, the expression of early growth response 1 (EGR1) and nuclear receptor superfamily 3, group C, member 1 (NR3C1), other transcriptional regulators involved in MT1 isomers, were increased regardless of treatment with PHMG or CMIT. These results suggest that MTF1 is an essential transcription factor for the induction of MT1B, MT1F, MT1G, and MT1H by PHMG but not by CMIT.

Evaluation of the long-term effect of polyhexamethylene guanidine phosphate in a rat lung model using conventional chest computed tomography with histopathologic analysis.

There have been no studies on the effects of polyhexamethylene guanidine phosphate (PHMG) after a long period of exposure in the rodent model. We aimed to evaluate long-term lung damage after PHMG exposure using conventional chest computed tomography (CT) and histopathologic analysis in a rat model. A PHMG solution was intratracheally administrated to 24 male rats. At 8, 26, and 52 weeks after PHMG instillation, conventional chest CT was performed in all rats and both lungs were extracted for histopathologic evaluation. At 52 weeks after PHMG instillation, four carcinomas had developed in three of the eight rats (37.5%). Bronchiolo-alveolar hyperplasia and adenoma were found in rats at 8, 26, and 52 weeks post-instillation. The number of bronchiolo-alveolar hyperplasia significantly increased over time (P-value for trend< 0.001). The severity of lung fibrosis and fibrosis scores significantly increased over time (P-values for trend = 0.002 and 0.023, respectively). Conventional chest CT analysis showed that bronchiectasis and linear density scores suggestive of fibrosis significantly increased over time (P-value for trend < 0.001). Our study revealed that one instillation of PHMG in a rat model resulted in lung carcinomas and progressive and irreversible fibrosis one year later based on conventional chest CT and histopathologic analysis. PHMG may be a lung carcinogen in the rat model.

Biometric characteristics of eyes with central serous chorioretinopathy.

PURPOSE: To investigate the biometric characteristics of eyes with idiopathic central serous chorioretinopathy (CSC). METHODS: Medical records of 52 consecutive patients with unilateral CSC were reviewed. Central serous chorioretinopathy was diagnosed using spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography. Data collected for comparison with fellow eyes were refractive error, biometric measurements using partial coherence interferometry, and SD-OCT parameters. RESULTS: Mean time from subjective symptom onset to initial visit was 8.3 ± 12.29 weeks. Mean axial length (AL) was shorter in CSC eyes than in fellow eyes by 0.24 ± 0.379 mm (P < 0.001), and mean anterior chamber depth (ACD) was shallower in CSC eyes than in fellow eyes by 0.03 ± 0.088 mm (P = 0.021). Central serous chorioretinopathy eyes also had thicker subfoveal choroidal thickness (CT) than fellow eyes by 34.0 ± 45.93 µm (P < 0.001). Differences in spherical equivalents between CSC and fellow eyes correlated with AL differences (r = -0.690, P < 0.001) and CT differences (r = 0.473, P = 0.001). On multiple linear regression analysis, the differences in ACD between CSC and fellow eyes were significantly correlated with AL differences (P = 0.032) and symptom duration (P = 0.019). CONCLUSIONS: Biometric characteristics such as AL and ACD were different between eyes with CSC and fellow eyes. Variations in biometry, which correlated with CT differences, might be related to differences in refractive errors between eyes.

Characteristics of cystoid spaces in type 2 idiopathic macular telangiectasia on spectral domain optical coherence tomography images.

PURPOSE: To investigate the morphologic and topographic characteristics of intraretinal cystoid spaces in eyes with Type 2 idiopathic macular telangiectasia (MacTel 2). METHODS: Using B-scan and en face images of eyes with MacTel 2 taken from a spectral domain optical coherence tomography database, the circularities and mean gray values of the cystoid spaces were measured to determine their boundaries and reflectivity. The characteristics of cystoid spaces in MacTel 2 eyes were compared with those in eyes with Type 1 idiopathic macular telangiectasia (MacTel 1), retinal vein occlusion, and diabetic macular edema, which are caused by vascular leakage. The cystoid spaces of en face optical coherence tomography images were matched with fluorescein angiographic images. RESULTS: The circularity of the cystoid spaces in B-scan and en face optical coherence tomography images of 16 eyes with MacTel 2 was lower than that of eyes with MacTel 1 (P = 0.004 and P = 0.003, respectively), retinal vein occlusion (P < 0.001 and P < 0.001, respectively), and diabetic macular edema (P < 0.001 and P < 0.001, respectively). The mean gray value ratio of the cystoid spaces of eyes with MacTel 2 was lower than that of eyes with MacTel 1 (P = 0.002) and diabetic macular edema (P < 0.001). In eyes with MacTel 2, the cystoid spaces were located in the foveal center or parafoveal area. CONCLUSION: Characteristics of cystoid spaces of eyes with MacTel 2 were different from those in eyes with MacTel 1, retinal vein occlusion, and diabetic macular edema. The irregular boundaries and low reflectivity of the cystoid spaces in MacTel 2 may represent the degenerative origin of the disease.

Effects of ginkgo biloba extract on cultured human retinal pigment epithelial cells under chemical hypoxia.

PURPOSE: To investigate the effects of Ginkgo biloba extract (GBE) on expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells under chemical hypoxia. MATERIALS AND METHODS: RPE cells (ARPE-19) were cultured in either untreated media (control group), media treated with 200 µM cobalt chloride (hypoxia group) or media treated with both 200 µM cobalt chloride and 100 µg/ml GBE (hypoxia + GBE group) for various amounts of time. HIF-1α and VEGF expression were compared between groups. HIF-1α and VEGF messenger RNA (mRNA) were quantified using real-time polymerase chain reaction (PCR). HIF-1α of extracted nuclei and VEGF of the media were quantified using enzyme-linked immunosorbent assay (ELISA). The expression of HIF-1α was also assessed with Western blot and immunocytochemistry. RESULTS: HIF-1α mRNA, VEGF mRNA, HIF-1α and VEGF levels were higher in the hypoxia group compared with the control group; however, real-time PCR revealed decreased expression of HIF-1α mRNA and VEGF mRNA in the hypoxia + GBE group compared with the hypoxia group. In the ELISA, the HIF-1α and VEGF protein concentrations also decreased with GBE treatment. Western blot and immunostaining showed that the intensity of HIF-1α signals in the hypoxia + GBE group was lower than that of the hypoxia group. CONCLUSION: GBE reduced HIF-1α and VEGF expression in RPE cells cultured under chemical hypoxia in vitro.

Morphologic characteristics of chronic macular hole on optical coherence tomography.

PURPOSE: To investigate the morphologic characteristics of chronic macular holes (MHs) using optical coherence tomography. METHODS: We retrospectively reviewed optical coherence tomographic images of consecutive patients who had been diagnosed with MH. Chronic MH was defined as MH that was observed without being surgically treated for at least 1 year. Optical coherence tomographic parameters were compared between chronic and acute MH. RESULTS: Thirteen eyes of 13 patients were classified as chronic MH, and 67 eyes of 67 patients were classified as controls. While the basal hole diameter of chronic MH was not different from that of controls (P = 0.146), the minimum hole diameter (781.8 µm) of chronic MH was larger than that of controls (448.4 µm; P < 0.001). The hole height and MH index were smaller in the chronic MH group (380.6 µm; 0.31) than in control group (469.9 µm, 0.53; P = 0.033, P = 0.003). Intraretinal fluid was less frequently observed in chronic MH than in controls (P < 0.001). Retinal pigment epithelial atrophy was only observed in chronic MH. CONCLUSION: Chronic MH has features distinct from those of acute symptomatic MH on optical coherence tomography. These findings provide useful insight for the differentiation of chronic MH from acute MH.

Technical note: improved ancient DNA purification for PCR using ion-exchange columns.

A novel method of ancient DNA (aDNA) purification was developed using ion-exchange columns to improve PCR-amplifiable DNA extraction from ancient bone samples. Thirteen PCR-resistant ancient bone samples aged 500-3,300 years were tested to extract aDNA using a recently reported, silica-based aDNA extraction method and an ion-exchange column method for the further purification. The PCR success rates of the aDNA extracts were evaluated for the amplification ability of the fragments of mitochondrial DNA, a high-copy DNA, and amelogenin, a low-copy DNA. The results demonstrate that the further purification of silica-based aDNA extracts using ion-exchange columns considerably improved PCR amplification. We suggest that the ion-exchange column-based method will be useful for the improvement of PCR-amplifiable aDNA extraction, particularly from the poorly preserved, PCR-resistant, ancient samples.