In Vivo Human Lacrimal Gland Imaging Using an Ultrasound Biomicroscopy.

PURPOSE: In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings. METHODS: The representative UBM findings of palpebral lobes in seven subjects (four with non-Sjögren dry eye syndrome, one with Sjögren syndrome, and two healthy subjects) were described in this study. To prolapse the palpebral lobe, the examiner pulled the temporal part of the upper eyelid in the superotemporal direction and directed the subject to look in the inferonasal direction. We scanned the palpebral lobes longitudinally and transversely using UBM. We used an Aviso UBM with a 50 MHz linear probe and ClearScan. RESULTS: In UBM of two healthy subjects, the echogenicity of the lacrimal gland was lower than that of the sclera and homogeneous. But the parenchyma of a patient with Sjögren dry eye syndrome was quite inhomogeneous compared to the healthy subjects. In two patients with dry eye syndrome, we were able to observe some lobules in the parenchyma. We could find excretory ducts running parallel at the surface of the longitudinal section in some subjects. In the longitudinal UBM scan of a subject, we observed a tubular structure at a depth of 1,500 µm that was considered a blood vessel. It ran from the superonasal to the inferotemporal direction. In a subject, we observed a large cyst beneath the conjunctiva. CONCLUSIONS: Lacrimal gland imaging using UBM has both advantages of optical coherence tomography and sonography, and could be useful for evaluating dry eye syndrome.

Accuracy of Toric Intraocular Lens Calculators with Predicted and Measured Posterior Corneal Astigmatism Across Different Types of Astigmatism.

INTRODUCTION: This study is a retrospective case series to compare the accuracy of the Barrett toric calculator using predicted posterior corneal astigmatism (PCA) and PCA measurements using swept-source optical coherence tomography (SS-OCT) and a Scheimpflug camera. This evaluation was conducted across different types of anterior and posterior astigmatism. METHODS: A total of 146 eyes from 146 patients implanted with toric intraocular lenses were included. Mean absolute prediction error, standard deviation of prediction error, and the percentage of eyes with prediction errors within ±0.50 diopters (D) were calculated using vector analysis. Biometric measurements were conducted using the IOLMaster 700 and Pentacam HR. A subgroup analysis was conducted based on the orientation of both anterior and posterior corneal astigmatism. RESULTS: The Barrett toric calculator with predicted PCA yielded the best results, with 78.1% having a prediction error ≤ 0.50 D, which was a significantly higher percentage than the Barrett formula with the two versions of measured PCA (P < 0.05). In the subgroup with a horizontally steep meridian PCA using the IOLMaster 700, the Barrett formula with predicted PCA yielded the best results, with 78.3% of cases having a prediction error of less than 0.5 D. This percentage was significantly higher than the other two measured PCA subgroups (P < 0.05). CONCLUSION: The Barrett toric formula with predicted PCA demonstrated a statistically significantly higher proportion of cases with a prediction error ≤ 0.5 D compared to the two measured PCA formulas (from the IOLMaster 700 or Pentacam). This trend persisted even when the posterior corneal astigmatism was horizontally steep.

Categorization of Meibomian Gland Dysfunction Using Lipid Layer Thickness and Meibomian Gland Dropout in Dry Eye Patients: A Retrospective Study.

PURPOSE: In the present study, we determined the prevalence of obstructive meibomian gland dysfunction (MGD), hyposecretory MGD, grossly normal MG, and hypersecretory MGD in patients with dry eye syndrome using lipid layer thickness (LLT) and MG dropout. METHODS: Eighty-eight patients with dry eye syndrome were included in the study. Patients were categorized into four groups according to the LLT and weighted total meiboscore. The proportion of patients in each group was calculated. The age, sex, Ocular Surface Disease Index, LLT, Schirmer, tear film breakup time, cornea stain, weighted total meiboscore, expressibility, and quality of meibum were compared between the four groups. RESULTS: Fifteen eyes (17.0%) had obstructive MGD, two eyes (2.3%) had hyposecretory MGD, 40 eyes (45.5%) had grossly normal MG, and 17 eyes (19.3%) had hypersecretory MGD. The obstructive MGD group was younger than the grossly normal MG group. In obstructive MGD, the ratio of men to women was higher than that of the other groups. However, Ocular Surface Disease Index, Schirmer, tear film breakup time, and corneal stain did not show statistically significant differences between the four groups. The meibum expressibility of the hyposecretoy MGD group was worse than those of the other groups. The meibum expressibility of the hyposecretoy MGD group was poor than those of the obstructive and hypersecretory MGD group. CONCLUSIONS: This categorization was expected to help determine the best treatment method for dry eye syndrome, according to the MG status.

Limbal epithelial stem cell sheets from young donors have better regenerative potential.

To investigate the stemness of limbal epithelial stem cell sheets in relation to the donor's age. Human limbal explants from cadaveric donors were set on human amniotic membrane scaffolds with the xeno-free medium. We evaluated limbal epithelial sheet size, expression of stem/progenitor cell markers, and colony formation efficiency from donors of different age groups (age ≤ 45, age 45-65, and age > 65). Expression of the proliferation marker Ki67, stem/progenitor cell markers p63α and ABCG2, cornea specific marker PANCK, and differentiation marker CK12 were evaluated. To determine the effect of donor age on the storage period of limbal explant sheets, the limbal explant outgrowth sheets were stored in 4 °C for 2 days and analyzed for JC-1, p63α, and PANCK with FACS on each day. From days 6 to 12, the outgrowth area of the limbal epithelial stem cell sheet was significantly larger in the age ≤ 45 groups (296 ± 54.7 mm2, day 9) compared to the other two age groups [age 45-65 group (278 ± 62.6 mm2), age > 65 group (257 ± 44.0 mm2), day 9] (p < 0.01). In terms of stemness, outgrowth cells from aged donors (age > 65) showed lower expression of stem/progenitor cell markers p63α and ABCG2 and decreased CFE compared to the other two groups. There were significantly more p63α+ cells in outgrowth cells in the age ≤ 45 group (18.2 ± 3.6%) compared to the age > 65 group (14.1 ± 4.6%; p < 0.01). Limbal explant outgrowth sheet on the age ≤ 45 group (32.7 ± 7.5%) had higher percentages of cells resisting staining by JC-1 compared with sheets under the age > 65 groups (25.7 ± 7.1%, p < 0.01) (JC-1low). Cells from the age ≤ 45 group showed a higher clonogenic capacity than those from the other two age groups (45 < Age ≤ 65 CFE ratio = 0.7 ± 0.16, p < 0.01; 65 < Age CFE ratio = 0.3 ± 0.06, p < 0.01, vs. Age ≤ 45). In the age > 65 group, positive cells of p63α on D0, 1, and 2 were significantly lower compared to those in the age ≤ 45 group on the storage period (p < 0.01, respectively). Our results imply that donors younger than 65 years of age are a better source of limbal epithelial stem cell sheet generation with high regeneration potential.

Diquafosol ophthalmic solution enhances mucin expression via ERK activation in human conjunctival epithelial cells with hyperosmotic stress.

Purpose: To evaluate the effect of diquafosol tetrasodium on the expression of secretory and membrane-associated mucins in multi-layered cultures of primary human conjunctival epithelial cells (HCEC) using intracellular extracellular signal regulated kinase (ERK) signaling. Methods: HCECs were treated with hyperosmotic stress (400 mOsm/l) for 24 h after air-liquid interface cell culture followed by treatment with diquafosol. HCECs were stimulated for 1 h with or without PD98059, an ERK inhibitor, then treated with diquafosol for 6 h and 24 h. Mucin 1 (MUC1), mucin 16 (MUC16), and MUC5AC mRNA and protein expression levels were analyzed, and cell viability was detected using an MTT assay. Western blot analysis was used to examine p44/42 MAPK (Erk1/2) and phosphorylated p44/42 MAPK (Erk1/2) expression. Results: Hyperosmotic stressed HCECs demonstrated increased MUC5AC secretion and gene expression when treated with diquafosol. MUC1 mRNA levels increased significantly at 24 h (p<0.01), and expression of MUC16 mRNA levels increased at 6 h and were maintained until 24 h (p<0.05).There was no significant difference in cell viability compared to the control group. Immunostaining results for MUC1, MUC16, and MUC5AC in diquafosol tetrasodium-treated HCECs at 24 h showed more positive cells than in the control group. Phosphorylation of p44/42 MAPK (Erk1/2) signaling molecules significantly increased from 5 min to 60 min (p<0.05). The effects of diquafosol on mucin expressions in hyperosmotic stressed HCECs were significantly inhibited by PD98059, an ERK inhibitor, at 6 h and 24 h. Conclusions: ERK signaling may regulate the expression levels of MUC1, MUC16, and MUC5AC induced by diquafosol in hyperosmotic stressed HCECs.

Comparative Accuracy of Barrett Toric Calculator With and Without Posterior Corneal Astigmatism Measurements and the Kane Toric Formula.

PURPOSE: To compare the accuracy of the Barrett toric calculator with and without posterior corneal astigmatism and the Kane toric calculator. DESIGN: Retrospective cross-sectional study. METHODS: The study included a total of 79 eyes of 79 patients who underwent toric intraocular lens (IOL) insertion during uncomplicated cataract surgery by a single surgeon. Using vector analysis, the mean absolute prediction error, the standard deviation of the prediction error, and the percentage of eyes with a prediction error within ±0.50 diopter (D), ± 0.75 D, and ± 1.00 D were calculated. The IOL Master 700 (Carl Zeiss Meditec AG, Jena, Germany) was used for measuring biometry including posterior corneal astigmatism. The main analysis was designed to provide the clinical outcomes with each formula using the postoperative keratometry values and the measured postoperative IOL axis. Real-world analysis was performed using the preoperative keratometry values and the intended IOL axis. RESULTS: There was no significant difference in mean absolute prediction errors calculated with 2 versions of the Barrett toric formula (predicted posterior corneal astigmatism and measured posterior corneal astigmatism) and the Kane toric formula (P > .05). The Barrett toric calculator with predicted and measured posterior corneal astigmatism yielded the best results, with 60.8% <0.50 D prediction error in the main analysis. In the real-world analysis, the Barrett toric calculator with predicted posterior corneal astigmatism showed the best result, with 53.2% <0.50 D prediction error. CONCLUSION: The Barrett toric formula with and without posterior corneal astigmatism measurements using the IOL Master 700 and the Kane toric formula yielded accurate and comparable outcomes in this single-surgeon analysis. Am J Ophthalmol 2021;221:•••-•••. © 2021 Elsevier Inc. All rights reserved.

The Use of Conjunctival Staining to Measure Ocular Surface Inflammation in Patients With Dry Eye.

PURPOSE: To investigate the expression levels of inflammatory cytokines in the conjunctival epithelium and correlations with clinical parameters in dry eye disease (DED). METHODS: This study evaluated 28 patients with Sjögren syndrome (SS) DED, 28 patients with non-SS DED, and 10 controls. The messenger ribonucleic acid (mRNA) expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, IL-17, and matrix metalloproteinase 9 (MMP9) from conjunctival epithelium was investigated by real-time polymerase chain reaction. Protein expression was confirmed by immunofluorescence staining. Correlations were evaluated between the mRNA expression of inflammatory cytokines and clinical DED parameters such as ocular surface disease index score, Schirmer I value, tear film breakup time, and corneal and conjunctival staining scores. RESULTS: Patients with non-SS DED expressed significantly more IFN-γ, IL-6, and MMP9 genes in the conjunctival epithelium than the controls (P < 0.05), and all cytokine gene expression was significantly higher in patients with SS DED than in the controls (P < 0.01). Tumor necrosis factor-α, IL-1ß, IL-6, and IL-17 gene expression was higher in patients with SS DED than in the non-SS DED group (P < 0.05). Immunofluorescence staining of conjunctival epithelium demonstrated that positive cells with IL-6 or MMP9 were significantly higher in non-SS DED than in controls (P < 0.01) and much higher in SS DED than in non-SS DED (P < 0.05). Conjunctival staining scores significantly correlated with the expression of IFN-γ, IL-6, IL-17, and MMP9 in both DED groups (P < 0.05 in non-SS DED and P < 0.01 in SS-DED). Interestingly, correlation coefficients of all cytokines were much higher in SS DED compared to non-SS DED. Corneal staining scores showed positive correlations with IFN-γ, IL-17, and MMP9 (P < 0.05), and correlation coefficients were lower than those of conjunctival staining scores. CONCLUSIONS: Conjunctival staining scores may be useful to measure ocular surface inflammation in SS and non-SS DED.

Effect of anterior chamber depth on the choice of intraocular lens calculation formula.

PURPOSE: To investigate the effect of anterior chamber depth (ACD) on the refractive outcomes of the SRK/T, Holladay 1, Hoffer Q and Haigis formulae in short, normal, long and extremely long eyes. METHODS: This retrospective study involved patients who had uncomplicated cataract surgery. Preoperative axial length (AL) was divided into four subgroups: short (< 22.00 mm), normal (22.00-24.49 mm), long (24.50-25.99 mm), extremely long (≥ 26.00 mm). Preoperative ACD was divided into three subgroups: < 2.5, 2.50-3.49, and ≥ 3.5 mm. Median absolute errors (MedAEs) predicted by the SRK/T, Holladay 1, Hoffer Q and Haigis formulae were compared with the Friedman test. Post-hoc analysis involved the Wilcoxon signed rank test with a Bonferroni adjustment. Correlations between ACD and the predictive refractive errors of the four formulas were analyzed. RESULTS: In short eyes with an ACD < 2.5 mm, the Haigis formula revealed the highest MedAE. The difference in MedAE with the Hoffer Q formula (which had the lowest MedAE) was statistically significant (P = 0.002). In normal eyes, the Haigis formula significantly differed from the Holladay 1 (P = 0.002) and Hoffer Q (P = 0.005) formulae in the ACD < 2.5 mm group. In long eyes and extremely long eyes with an ACD ≥ 3.5 mm, the differences in MedAEs were statistically significant (P = 0.018, P = 0.001, respectively) and the Haigis formula had the lowest MedAEs in both subgroups (0.29 D, 0.30 D, respectively). In the total of 1,123 eyes, refractive errors predicted by the Haigis formula showed a significant negative correlation with the ACD (R2 = 0.002, P = 0.047). CONCLUSIONS: The Hoffer Q formula is preferred over other formulae in short eyes with an ACD shallower than 2.5 mm. In short and normal eyes with an ACD < 2.5 mm the Haigis formula might underestimate ELP. The Haigis formula is the preferred choice in eyes with an AL ≥ 24.5 mm and an ACD ≥ 3.5 mm.

Comparison of Anterior Capsule Stability Following Implantation of Three Single Piece Acrylic Intraocular Lenses with Different Haptic Design.

PURPOSE: To compare the anterior capsule contraction and intraocular lens (IOL) decentration among three types of IOL to determine the influence of haptic design on anterior capsule stability. METHODS: One hundred fifty patients were enrolled in this prospective, randomized study and 260 eyes underwent implantation of one of the following IOLs: modified L-haptic IOL (n = 74), modified C-haptic IOL (n = 97), or a plate-haptic IOL (n = 89). The area of the anterior capsule opening, IOL decentration, and capsule overlap were measured using retroillumination photospot 1 day and 2 months after cataract surgery. RESULTS: The area of capsule opening at postoperative day 1 was significantly different between the three IOLs (p < 0.01). All IOLs showed reduction of the anterior capsule opening from 1 day to 2 months after surgery, and greater reduction was shown in the modified C-haptic IOL (p < 0.001). At postoperative month 2, IOL decentration was significantly different between the IOLs and showed a positive correlation with the mean area reduction during month 2. CONCLUSIONS: The degree of anterior capsule contraction and IOL decentration in modified L-haptic IOLs were less than those in modified C-haptic IOLs and comparable to those in plate-haptic IOLs.

Association Between Migraine and Dry Eye Disease: A Nationwide Population-Based Study.

PURPOSE: Despite the possible association between migraine and dry eye disease (DED), there are only a few studies investigating this link in a relatively limited number of patients. Therefore, we have analyzed the relationship between migraine and DED in the Korean population. MATERIALS AND METHODS: This population-based cross-sectional study included 14 329 adults participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2012. Migraine, DED diagnosis, and DED symptoms were assessed using questionnaires and surveys. Data were analyzed using logistic regression to determine the association of migraine with DED while controlling for demographic, lifestyle, and medical factors. RESULTS: Individuals with migraine were more likely to report a DED diagnosis (14.4% vs. 8.2%, p < 0.0001) and DED symptoms (22.0% vs. 15.1%, p < 0.0001). In a multivariate analysis, the association between migraine and DED diagnosis was significant after adjustments (OR, 1.577; 95% CI, 1.340-1.855). The association between migraine and DED symptoms showed a similar pattern (OR, 1.304; 95%CI, 1.151-1.502). CONCLUSIONS: Although a causal relationship was not revealed, we found that patients who had a lifetime history of migraine were more likely to suffer from DED than individuals who did not present with headaches; this association may require confirmation. Large prospective cohort studies are required to evaluate the association between migraine and DED, as well as the influence of DED treatment on the frequency and severity of migraine attacks.