Reliability of human retina organoid generation from hiPSC-derived neuroepithelial cysts.

The possible applications for human retinal organoids (HROs) derived from human induced pluripotent stem cells (hiPSC) rely on the robustness and transferability of the methodology for their generation. Standardized strategies and parameters to effectively assess, compare, and optimize organoid protocols are starting to be established, but are not yet complete. To advance this, we explored the efficiency and reliability of a differentiation method, called CYST protocol, that facilitates retina generation by forming neuroepithelial cysts from hiPSC clusters. Here, we tested seven different hiPSC lines which reproducibly generated HROs. Histological and ultrastructural analyses indicate that HRO differentiation and maturation are regulated. The different hiPSC lines appeared to be a larger source of variance than experimental rounds. Although previous reports have shown that HROs in several other protocols contain a rather low number of cones, HROs from the CYST protocol are consistently richer in cones and with a comparable ratio of cones, rods, and Müller glia. To provide further insight into HRO cell composition, we studied single cell RNA sequencing data and applied CaSTLe, a transfer learning approach. Additionally, we devised a potential strategy to systematically evaluate different organoid protocols side-by-side through parallel differentiation from the same hiPSC batches: In an explorative study, the CYST protocol was compared to a conceptually different protocol based on the formation of cell aggregates from single hiPSCs. Comparing four hiPSC lines showed that both protocols reproduced key characteristics of retinal epithelial structure and cell composition, but the CYST protocol provided a higher HRO yield. So far, our data suggest that CYST-derived HROs remained stable up to at least day 200, while single hiPSC-derived HROs showed spontaneous pathologic changes by day 200. Overall, our data provide insights into the efficiency, reproducibility, and stability of the CYST protocol for generating HROs, which will be useful for further optimizing organoid systems, as well as for basic and translational research applications.

Influence of Different Antidepressants on Ocular Surface in Patients With Major Depressive Disorder.

PURPOSE: Several studies have previously reported the association between dry eye and depression along with the treatment of depression. The aim of this study was to investigate the effects of different antidepressant drugs on tear parameters in patients with major depressive disorder. METHODS: We recruited 132 patients who were using different antidepressants and 58 healthy controls. Venlafaxine, duloxetine, escitalopram, and sertraline were used by 34, 28, 36, and 34 patients, respectively. The participants filled out and completed the Beck Depression Scale. We recorded Schirmer test, tear breakup time (TBUT) and corneal staining values of the participants. The Ocular Surface Disease Index was completed by the participants. In addition, we evaluated the tear meniscus parameters by using anterior segment optical coherence tomography. RESULTS: All conventional dry eye tests and tear meniscus parameters were significantly lesser in the depression group than in the control group (Schirmer test, 11.41 ± 6.73 mm and 22.53 ± 4.98 mm; TBUT, 5.29 ± 2.92 seconds and 13.38 ± 1.72; Corneal staining, tear meniscus area, 0.026 ± 0.012 mm2 and 0.11 ± 0.025 mm2; tear meniscus depth, 182.75 ± 78.79 µm and 257.48 ± 90.1 µm; tear meniscus height, 290.3 ± 133.63 µm and 459.78 ± 180.26 µm, in patients and controls, respectively). The tear parameters of the duloxetine group were lowest among the drug groups and Schirmer test, and TBUT of the venlafaxine group was statistically significantly different from the duloxetine group (P = 0.028 and P = 0.017, respectively). Ocular Surface Disease Index score of the depression group was significantly higher than the control group (31.12 ± 21.15 and 17.43 ± 11.75 in depression and control group, respectively.). CONCLUSIONS: We found that the usage of selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors affects the ocular surface by a mechanism other than the anticholinergic system. Besides serotonin blockage, the noradrenaline blockade of serotonin noradrenaline reuptake inhibitors may increase the dry eye findings on the ocular surface.

Effects of Temperamental Characteristics on Depression-Anxiety Levels and the Quality of Life in Infertile Women.

OBJECTIVE: It is known that the risk of anxiety disorders and depression in infertile women increases and their quality of life deteriorates. Temperamental characteristics are considered as predictors of mood disorders. The aim of this study was to investigate temperamental characteristics in infertile women and their effects on depression and anxiety levels, and the quality of life, and to reveal the differences and level of relationship compared to healthy women. METHOD: Fourty-four female patients with primary infertility and 30 healthy female controls were included in this study. Temperamental characteristics of the participants were assessed with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version (TEMPS-A). Depression and anxiety severity were evaluated with Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). To evaluate the quality of life, Short Form 36 (SF-36) health survey questionnaire was also applied. RESULTS: Hyperthymic temperament scores were higher in infertile women than the control group (p=0.001). BDI scores were positively correlated with depressive and cyclothymic temperament scores, and BAI scores were positively correlated with depressive and anxious temperament scores. A negative correlation was found between hyperthymic temperament and BAI and BDI scores. Hyperthymic temperament scores were positively correlated with both physical and mental subdimension scores of the quality of life scale. CONCLUSION: In this study, hyperthymic temperament in infertile women was shown to be protective against anxiety and depression and it also improves the quality of life. Additional studies are needed to clarify the relationship between hyperthymic temperament and ovarian hormones or other biological parameters.

Facial emotion recognition deficits in patients with bipolar disorder and their healthy parents.

BACKGROUND: There is evidence on deficits in facial emotion recognition (FER) in patients with bipolar disorder (BD), and these deficits may be present in individuals with genetic risk for BD. This study investigated facial emotion identification and discrimination abilities in patients with BD, their parents, and healthy controls. MATERIALS AND METHODS: This study included 38 patients with bipolar I disorder and 30 healthy controls for patients as well as 30 healthy mothers and 30 healthy fathers of these patients and 30 healthy controls who matched the mothers and fathers for age, gender, and education (total 188 participants). Facial Emotion Identification and Discrimination Tests were applied to all participants; the Hamilton Depression Rating Scale and Young Mania Rating Scale were applied to patients and their control group. RESULTS: Facial Emotion Identification and Discrimination Test scores of patients and their parents were reasonably lower than their matching control groups. Moreover, we found that difficulty in FER affected more emotions in mothers than in fathers and mothers performed significantly worse than patients in the identification of angry and embarrassed faces. CONCLUSION: These findings indicate that parents of patients with BD have impairment with recognizing facial emotions and suggest that there may be an association between FER of patients with BD and that of their mothers.

Optical coherence tomography angiography findings of multiple sclerosis with or without optic neuritis.

Objective: Nowadays, retinal microvascular structures can be investigated using optical coherence tomography angiography (OCTA). We aimed to evaluate the probable vascular changes in the foveal and peripapillary regions of patients with multiple sclerosis (MS).Methods: A total of 20 patients with relapsing remitting multiple sclerosis (RRMS) and 24 healthy controls were recruited in this study. All participants' superficial and deeper retinal and peripapillary layers were evaluated using OCTA after a total ophthalmologic examination.Results: In the superficial plexus, the whole image (49.53 ± 3.9% and 51.83 ± 2.1%, p = 0.009), superior hemisphere (49.44 ± 4.11% and 51.63 ± 2.3%, p = 0.018), inferior hemisphere (49.75 ± 3.9% and 52.03 ± 2.2%, p = 0.012), parafoveal (51.87 ± 3.9% and 53.08 ± 3.46%, p = 0.048) and perifoveal (50.41 ± 3.86% and 52.76 ± 2.1%, p = 0.007) vascular densities were statistically significant lesser in patients with RRMS than in controls. In the optic disc OCTA parameters, the vessel density of the inferior (50.15 ± 6.99% and 53.04 ± 3.63% p = 0.043) and temporal sector (48.09 ± 5.47% and 50.85 ± 5.24%, p = 0.045) were statistically significantly lesser in patients with RRMS than in controls.Conclusion: The reductions in vessel density of the retinal or peripapillary area of patients with RRMS shown in this study should be investigated further to determine whether it is a secondary lesion to optic neuritis (ON) or a primary vasculopathic condition of MS.

Relationship Among Coping Strategies, Quality of Life, and Anxiety and Depressive Disorders in Hemodialysis Patients.

Patients with hemodialysis face many physical and emotional stressors; yet little is known regarding coping strategies and their effects on patients' quality of life (QOL) and anxiety and depressive disorders. A total of 117 patients were enrolled in this cross-sectional study between October 2016 and April 2017. This study assessed QOL (Medical outcome short form 36-MOS 36), coping (Assessment Scale for Coping Attitudes-COPE) and psychiatric comorbidities in hemodialysis patients. Beck Depression Scale and Beck Anxiety Scale were also applied. Differences between groups were evaluated using Student's t-tests and anova. Correlations among parameters were performed. Patients with any depressive disorder (22.2%, n = 26) and patients with any anxiety disorder (19.6%, n = 23) reported more impaired QOL. The most frequently used coping strategy in all patients was religious coping. Use of instrumental social support, humor, and positive reinterpretation scores were lower in patients with any depressive disorder (P = 0.009, P = 0.034, P = 0.047).The total score of emotion-focused coping strategies was lower with patients with any depressive disorder (P = 0.021) and emotion-focused coping strategies were positively correlated with QOL scores. Younger age and longer duration of hemodialysis have significant negative correlation with emotion-focused coping strategies' total score (P = 0.01, P = 0.02). Patients with hemodialysis use variety of coping strategies. The use of emotion-focused coping was associated with better QOL and reducing the risk of depressive disorder. Interventions to facilitate the use of adaptive coping strategies may improve patients' QOL and mood.

Evaluation of affective temperament and anxiety-depression levels in fibromyalgia patients: a pilot study

Objective: Fibromyalgia (FM) patients have higher rates of depression and anxiety disorders than healthy controls. Affective temperament features are subclinical manifestations of mood disorders. Our aim was to evaluate the affective temperaments of FM patients and investigate their association with depression and anxiety levels and clinical findings. Methods: This cross-sectional study included FM patients and healthy controls. The Hospital Anxiety and Depression Scale (HADS) was used to determine patient anxiety and depression levels, and the Temperament Scale of Memphis, Pisa and San Diego, self-administered version was applied to assess affective temperaments in all subjects. Disease severity was assessed in FM patients with the Fibromyalgia Criteria and Severity Scales and the Fibromyalgia Impact Questionnaire (FIQ). Differences between groups were evaluated using Student's t-tests. Correlations among parameters were performed. Results: This study involved 38 patients with FM (30 female) and 30 healthy controls (25 female). Depressive, anxious and cyclothymic temperaments were significantly higher in FM patients than healthy controls. Statistically significant positive correlations were found between HADS depression score and all temperaments except hyperthymic, as well as between HADS anxiety score and cyclothymic and anxious temperaments. HADS depression and anxiety scores were correlated with symptom severity. We found a higher risk of depression and anxiety among FM patients with higher FIQ scores. Conclusion: This study is the first to evaluate affective temperament features of FM patients. Evaluating temperamental traits in FM patients may help clinicians determine which patients are at risk for depression and anxiety disorders.

Evaluation of dry eye disease in newly diagnosed anxiety and depression patients using anterior segment optical coherence tomography.

BACKGROUND: We aimed to evaluate dry eye diseases (DED) in patients with newly diagnosed depression and anxiety patients. METHODS: Forty newly diagnosed depression, 35 anxiety patients, and 37 controls without any history of taking psychiatric drugs (or before the beginning of psychiatric medication) and topical ophthalmic drop use, were included in the study. All depression and anxiety diagnoses were performed by an experienced psychiatrist. Beck depression and anxiety tests were used to measure disease severity. Tear film break up time (TBUT), Schirmer's test, Oxford scores and ocular surface disease index (OSDI) were admiinistered to participants. Anterior segment optical coherence tomography was used to measure tear meniscus heights (TMH), tear meniscus depths (TMD) and tear meniscus areas (TMA). RESULTS: In anxiety and depression groups, Schirmer's test (mm) (7.24 ± 6.02, 6.58 ± 4.9 and 18.79 ± 4.9 respectively, p < 0.05) and TBUT (s) (5.62 ± 3.1, 5.6 ± 3.5 and 13.37 ± 1.7 respectively, p < 0.05) were significantly lower than control group. In addition, OSDI and Oxford scores were significantly higher than controls. OSDI scores were 28.01 ± 19, 30.43 ± 18.49, 14.38 ± 8.14 respectively (p = 0.002) and Oxford scores were 1.9 ± 0.7, 2.1 ± 0.6 and 0.7 ± 0.4 respectively (p = 0.001). TMD, TMH and TMA values were significantly lower in anxiety and depression groups compared with control groups. Correlations between disease inventory scores and dry eye tests were detected. CONCLUSIONS: This study showed a relation between DED and newly diagnosed anxiety and depression patients with no history of psychiatric drug use. The presence of correlation between dry eye tests and disease inventory scores strengthens this association. This is an important knowledge that need to be evaluated in these patients before starting psychiatric medication.

Evaluation of affective temperament and anxiety-depression levels in fibromyalgia patients: a pilot study.

OBJECTIVE: Fibromyalgia (FM) patients have higher rates of depression and anxiety disorders than healthy controls. Affective temperament features are subclinical manifestations of mood disorders. Our aim was to evaluate the affective temperaments of FM patients and investigate their association with depression and anxiety levels and clinical findings. METHODS: This cross-sectional study included FM patients and healthy controls. The Hospital Anxiety and Depression Scale (HADS) was used to determine patient anxiety and depression levels, and the Temperament Scale of Memphis, Pisa and San Diego, self-administered version was applied to assess affective temperaments in all subjects. Disease severity was assessed in FM patients with the Fibromyalgia Criteria and Severity Scales and the Fibromyalgia Impact Questionnaire (FIQ). Differences between groups were evaluated using Student's t-tests. Correlations among parameters were performed. RESULTS: This study involved 38 patients with FM (30 female) and 30 healthy controls (25 female). Depressive, anxious and cyclothymic temperaments were significantly higher in FM patients than healthy controls. Statistically significant positive correlations were found between HADS depression score and all temperaments except hyperthymic, as well as between HADS anxiety score and cyclothymic and anxious temperaments. HADS depression and anxiety scores were correlated with symptom severity. We found a higher risk of depression and anxiety among FM patients with higher FIQ scores. CONCLUSION: This study is the first to evaluate affective temperament features of FM patients. Evaluating temperamental traits in FM patients may help clinicians determine which patients are at risk for depression and anxiety disorders.

Choroidal thickness in patients with fibromyalgia and correlation with disease severity.

PURPOSE: To evaluate and compare choroidal thickness in patients with fibromyalgia (FM) and healthy controls. METHODS: In this prospective, cross-sectional study, forty eyes of 40 patients with FM and 40 eyes of 40 age- and sex-matched healthy subjects were enrolled. FM was diagnosed according to the American College of Rheumatology criteria. The choroidal thickness measurements of the subjects were obtained using spectral-domain optical coherence tomography (RTVue-100, Optovue). Widespread pain index (WPI), symptom severity scale (SSS), and fibromyalgia impact questionnaire (FIQ) scores were recorded. The choroidal thickness measurements of the groups were compared, and correlations among the WPI, SSS, and FIQ scores and these measurements were calculated. RESULTS: Choroidal thicknesses at 1500 µm nasally were 198.5 ± 46.7 µm and 306.3 ± 85.4 µm; at 1000 µm nasally were 211.7 ± 50.2 µm and 310.05 ± 87.26 µm; at 500 µm nasally were 216 ± 55.05 µm and 311.5 ± 83.4 µm; at subfoveal region were 230.9 ± 58.4 µm and 332.4 ± 91.3 µm; at 500 µm temporally 227.5 ± 58.1 µm and 318.15 ± 92.3 µm; at 1000 µm temporally 224.5 ± 57.07 µm and 315.1 ± 84.2 µm; at 1500 µm temporally 212.5 ± 56.08 µm and 312.9 ± 87.8 µm in the FM and control groups, respectively (P < 0.001). Choroidal thicknesses were thinner at all measurement location, except temporal 1000 and 1500 in patients with FIQ score ≥50 than in FIQ score <50. CONCLUSION: The results of this study demonstrated that choroidal thickness decreases in patients with FM and correlated with disease activity. This choroidal changes might be related with the alterations in autonomic nervous system functioning. Further studies are needed to evaluate the etiopathologic relationship between choroidal thickness and FM.