Glaucoma and the ocular renin-angiotensin-aldosterone system: Update on molecular signalling and treatment perspectives.

Glaucoma, a leading cause of blindness worldwide, encompasses a group of pathological conditions affecting the optic nerve and is characterized by progressive retinal ganglion cell loss, cupping of the optic nerve head, and distinct visual field defects. While elevated intraocular pressure (IOP) is the main risk factor for glaucoma, many patients do not have elevated IOP. Consequently, other risk factors, such as ocular blood flow abnormalities and immunological factors, have been implicated in its pathophysiology. Traditional therapeutic strategies primarily aim to reduce IOP, but there is growing interest in developing novel treatment approaches to improve disease management and reduce the high rates of severe visual impairment. In this context, targeting the ocular renin-angiotensin-aldosterone system (RAAS) has been found as a potential curative strategy. The RAAS contributes to glaucoma development through key effectors such as prorenin, angiotensin II, and aldosterone. Recent evidence has highlighted the potential of using RAAS modulators to combat glaucoma, yielding encouraging results. Our study aims to explore the molecular pathways linking the ocular RAAS and glaucoma, summarizing recent advances that elucidate the role of the RAAS in triggering oxidative stress, inflammation, and remodelling in the pathogenesis of glaucoma. Additionally, we will present emerging therapeutic approaches that utilize RAAS modulators and antioxidants to slow the progression of glaucoma.

Short-Term Clinical Outcomes of Patients with Diabetic Macular Edema Following a Therapy Switch to Faricimab.

Background: With this study, we investigate the short-term clinical outcomes of patients affected by diabetic macular edema (DME) after switching to intravitreal Faricimab (IVF) in a real-world setting. Methods: We conducted a retrospective chart review on all patients treated for DME with IVF who showed insufficient responses to prior anti-VEGF therapy. Data collected included baseline patient demographics, medical history, best-corrected visual acuity (BCVA), central retinal thickness (CRT) and central retinal volume (CRV). We analyzed functional and structural measures before and after IVF, compared baseline demographics and treatment factors between Faricimab-responders and reduced-responders and assessed influencing factors of the follow-up BCVA and CRT. Results: This study included 25 eyes from 16 patients. After switching to IVF, the mean BCVA showed no significant improvement, changing from 59.4 ± 13.4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at baseline to 61.4 ± 12.8 ETDRS letters at follow-up (p = 0.26). CRT significantly reduced from 414.4 ± 126.3 µm to 353.3 ± 131.1 µm (p < 0.011), and the 3 mm CRV significantly decreased from 2.8 ± 0.5 mm3 to 2.6 ± 0.6 mm3 (p < 0.012). Seven patients met the responder criteria, exhibiting an improvement of at least 5 ETDRS letters and a simultaneous CRT reduction of at least 30 µm. Further analysis showed that higher BCVA at baseline (p < 0.001) was associated with better BCVA following IVF, while higher baseline CRT (p < 0.003), a higher number of prior anti-VEGF agents (p < 0.034) and prior corticosteroid injections (p < 0.019) were associated with greater CRT at follow-up. Conclusions: Following the initial IVF injection series, we observed a clear improvement of anatomical measures. No functional improvement was observed, although visual acuity remained stable. Higher baseline BCVA was associated with better post-IVF BCVA, while higher baseline CRT, a greater number of prior anti-VEGF agents and prior corticosteroid injections were linked to higher CRT post-IVF.

Utility of a Model to Predict Endothelial Cell Density of Donor Corneas to Determine Suitability for Transplantation.

Purpose: In Germany, approximately one-third of the harvested donor corneas are not suitable for transplantation, mostly due to insufficient endothelial cell density (ECD). The ECD can only be reliably determined after harvesting and processing of the cornea. Our group has previously developed a predictive model for corneal ECD: \( {Predicted\, ECD} = 2919-6^{\ast}\;{age}\; [{years}]-189\; [{if\, male}]\\ -7^{\ast}\;{death-to-explantation\, interval\,} [{hours}]\\ - 378\; [{if\, pseudophakic}] \;{cells/mm}^2 \). Methods: A total of 2.999 consecutive donor corneas harvested between 2017 and 2021 from the Eye Bank of Rhineland-Palatinate in Mainz, Germany, were included. An actual ECD of >2000 cells/mm2 was defined as the cutoff value. To evaluate the clinical utility of the prognostic model as a screening instrument for transplant eligibility in an independent cohort, we performed a decision curve analysis. Results: The median predicted ECD was 2061 cells/mm2 (interquartile range [IQR] = 1834 to 2221), whereas the median actual ECD was 2377 cells/mm2 (IQR = 1907 to 2624). There was a positive correlation between predicted and actual ECD (correlation coefficient = 0.411; P < 0.01). Our predictive model for ECD is a strong predictor for an actual ECD greater than 2000 (odds ratio = 1.374, 95% confidence interval [CI]) per 100 cells; P < 0.001, area under the curve [AUC] of 0.73). Decision curve analysis showed that the predictive model yielded a positive net benefit in clinical settings. Conclusions: Decision curve analysis demonstrated a positive net benefit of the ECD predictive model in clinical settings with limited eye bank resources. Translational Relevance: In possible scenarios where a choice between corneal grafts is required, or in countries with limited eye bank infrastructure and staff, the initial estimate of ECD from the formula may be beneficial.

Hypertensive Retinopathy is Not Associated with Low or High Birth Weight - Results from the Population-Based German Gutenberg Health Study.

This study investigates the association between self-reported birth weight (BW) and the prevalence of hypertensive retinopathy (HR) in a large population-based cohort in Germany, as part of the Gutenberg Health Study (GHS). The study involved analyzing fundus photographs of 6855 participants, aged 35 to 74, to assess signs of HR, classified according to the Mitchell-Wong Classification. The research aimed to explore the correlation between fetal growth restriction indicated by BW and the frequency of HR. The results showed that the frequency of HR did not significantly differ among groups with different BW ranges. In the univariable analysis, HR was initially associated with high BW, but this association disappeared after adjusting for age, sex, and cardiovascular risk factors. No association was found between low BW and HR. The study reveals novel insights as there are no prior population-based studies specifically exploring this association.

Sex-Specific Differences in the Relationship Between Prematurity and Ocular Geometry.

Purpose: To explore differences in the relationship between gestational age (GA) and birth weight (BW) percentile and ocular geometry between males and females. Methods: The Gutenberg Prematurity Eye Study involved a prospective ophthalmic examination of adults, aged 18 to 52 years, who were born preterm or at term, in Germany. The associations between GA and BW percentile on the main outcome measures were evaluated by uni- and multivariable linear regression analyses. The main outcome measures were central corneal thickness, corneal radius, anterior chamber depth, lens thickness, posterior segment length, and central foveal thickness. Potential sex-specific differences and an effect modification by sex were analyzed. Results: This study involved 438 participants (245 females, 193 males) with an average age of 28.6 ± 8.7 years. In female participants, central foveal thickness was negatively associated with a higher GA (B = -2.99; P < 0.001). Similarly, male participants also demonstrated a negative association between central foveal thickness and GA (B = -4.27; P < 0.001). The multivariable model with effect modification revealed that the central foveal thickness was thicker with lower GA. There was an association between the effect modification of GA with sex and central foveal thickness, demonstrating a more pronounced effect of GA on central foveal thickness in male participants (B = 1.29; P = 0.04). Conclusions: This study identified a sex-specific correlation between lower GA and thicker central foveal thickness, suggesting differences in the developmental trajectory of this biometric parameter concerning GA. A thicker central foveal thickness might affect the visual acuity of individuals born preterm in adulthood, with a more pronounced impact in males and a potential predisposition to age-related diseases later in life. Sex did not influence the association of GA or BW percentile to other ocular geometric parameters.

Characteristics and Treatment Outcomes of Hypotony Maculopathy Post-Glaucoma Filtering Surgery: An Optical Coherence Tomography-Based Study.

PURPOSE: This study assesses morphological characteristics using SD-OCT in patients with hypotony maculopathy (HM) following glaucoma filtering surgery and evaluates the results of its treatment. MATERIAL AND METHODS: Retrospective analysis of all HM patients between January 2019 and March 2023. Inclusion criteria consisted of both pre-operative and post-revision SD-OCT images of the macula and the presence of HM as observed on OCT images preoperatively. HM was graded according to its appearance in OCT both pre- and post-revision surgery. Change in visual acuity and IOP were assessed. RESULTS: 45 eyes of 45 patients were included. 21 eyes had HM limited to retinal pigment epithelium (RPE), 18 eyes had involvement of RPE and photoreceptor layers and 6 eyes had additional intra- or subretinal edema. After revision surgery with IOP elevation, 64% of eyes had complete HM regression with no HM signs in OCT imaging. 80% of patients achieved at least one grade improvement in HM. Preoperative visual acuity increased from 0.7±0.4 (logMAR) to 0.4±0.4 at 2 weeks postoperatively, over the course of an increase of IOP from 3.5±1.8 mmHg to 17.1±10.6 mmHg at day one. Eyes with complete HM regression had higher IOP at day 1 compared to those without improvement (P=0.04). The median time between HM onset and revision was 10.0 days for those with complete regression and 27 days for those without improvement (P=0.04). CONCLUSIONS: Bleb revision procedures for HM following glaucoma filtering surgery show promising outcomes, including notable improvements in visual acuity and IOP. The timing of revision surgery appears to influence outcome. In our study earlier intervention was associated with better results. Even delayed surgeries can lead to an improvement, although complete morphological restoration may not be achieved in advanced grades of HM.

Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms.

Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-ß inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.

The Effect of Trabecular Aspiration on Intraocular Pressure, Medication and the Need for Further Glaucoma Surgery in Eyes with Pseudoexfoliation Glaucoma.

PURPOSE: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. METHODS: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment. RESULTS: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA. CONCLUSIONS: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients.

Neuroretinal Cell Culture Model as a Tool for the Development of New Therapeutic Approaches for Oxidative Stress-Induced Ocular Diseases, with a Focus on Glaucoma.

Glaucoma is a heterogeneous group of optic neuropathies characterized by a progressive degeneration of the retinal ganglion cells (RGCs), leading to irreversible vision loss. Nowadays, the traditional therapeutic approach to glaucoma consists of lowering the intraocular pressure (IOP), which does not address the neurodegenerative features of the disease. Besides animal models of glaucoma, there is a considerable need for in vitro experimental models to propose new therapeutic strategies for this ocular disease. In this study, we elucidated the pathological mechanisms leading to neuroretinal R28 cell death after exposure to glutamate and hydrogen peroxide (H2O2) in order to develop new therapeutic approaches for oxidative stress-induced retinal diseases, including glaucoma. We were able to show that glutamate and H2O2 can induce a decrease in R28 cell viability in a concentration-dependent manner. A cell viability of about 42% was found after exposure to 3 mM of glutamate and about 56% after exposure to 100 µM of H2O2 (n = 4). Label-free quantitative mass spectrometry analysis revealed differential alterations of 193 and 311 proteins in R28 cells exposed to 3 mM of glutamate and 100 µM of H2O2, respectively (FDR < 1%; p < 0.05). Bioinformatics analysis indicated that the protein changes were associated with the dysregulation of signaling pathways, which was similar to those observed in glaucoma. Thus, the proteomic alteration induced by glutamate was associated with the inhibition of the PI3K/AKT signaling pathway. On the other hand, H2O2-induced toxicity in R28 cells was linked to the activation of apoptosis signaling and the inhibition of the mTOR and ERK/MAPK signaling pathways. Furthermore, the data show a similarity in the inhibition of the EIF2 and AMPK signaling pathways and the activation of the sumoylation and WNT/ß-catenin signaling pathways in both groups. Our findings suggest that the exposure of R28 cells to glutamate and H2O2 could induce glaucoma-like neurodegenerative features and potentially provide a suitable tool for the development of new therapeutic strategies for retinal diseases.

Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress.

Acknowledged as a significant pathogenetic driver for numerous diseases, aging has become a focal point in addressing the profound changes associated with increasing human life expectancy, posing a critical concern for global public health. Emerging evidence suggests that factors influencing vascular aging extend their impact to choroidal and retinal blood vessels. The objective of this work is to provide a comprehensive overview of the impact of vascular aging on ocular blood vessels and related diseases. Additionally, this study aims to illuminate molecular insights contributing to vascular cell aging, with a particular emphasis on the choroid and retina. Moreover, innovative molecular targets operating within the domain of ocular vascular aging are presented and discussed.

FOVEAL AVASCULAR ZONE IN ADULTS BORN PRETERM WITH AND WITHOUT RETINOPATHY OF PREMATURITY: Results From The Gutenberg Prematurity Eye Study.

PURPOSE: To examine potential changes in the foveal avascular zone (FAZ) during adulthood due to prematurity and retinopathy of prematurity (ROP), as assessed by measurements of the FAZ area and circularity. METHODS: The Gutenberg Prematurity Eye Study is a retrospective German cohort study with a prospective ophthalmologic examination of adults aged 18 years to 52 years, born either preterm or full-term, using spectral-domain optical coherence tomography angiography. Participants were categorized into groups based on gestational age and postnatal ROP status. The study conducted multivariable linear regression analyses to explore associations with the FAZ. RESULTS: The study cohort comprised 380 right eyes from individuals born both preterm and full-term, with an average age of 28.4 years ± 8.6 years, including 214 women. The FAZ area decreased as gestational age decreased: FAZ was 0.28 mm 2 ± 0.12 mm 2 in the control group, 0.21 ± 0.10 mm 2 at GA 33 weeks to 36 weeks, 0.18 mm 2 ± 0.10 mm 2 at GA 29 weeks to 32 weeks, 0.11 mm 2 ± 0.10 mm 2 at GA ≤28 weeks, 0.11 mm 2 ± 0.10 mm 2 in ROP without treatment, and 0.11 mm 2 ± 0.10 mm 2 in those requiring ROP treatment. In the multivariable analyses, smaller FAZ was independently associated with gestational age ( P < 0.05), increased foveal retinal thickness ( P < 0.05), and foveal hypoplasia ( P < 0.05). Moreover, no association was seen between visual acuity and FAZ. CONCLUSION: The main perinatal factor associated with a smaller FAZ in this German cohort is preterm birth, while ROP, ROP treatment, or other perinatal factors do not affect FAZ observed in adulthood. A smaller FAZ shape in preterm individuals might be an indicator of foveal hypoplasia.

Recalled Maternal Rearing Behaviour of Individuals Born Preterm and Their Mothers: The Impact of Intimate Mother-Child Contact.

Background: Preterm birth is a risk factor for a variety of detrimental health outcomes. Previous studies have identified recalled (or remembered) parental rearing behaviour as a potential modifier of preterm individuals' mental health in adulthood. However, no investigations to date have contrasted the parents' and children's views, explored whether their congruence is associated with preterm individuals' mental health, or tested associations with maternal self-reported first skin-on-skin contact. Methods: This cohort study involved 199 participants of the Gutenberg Prematurity Eye Study (GPES), with prospective clinical examination and psychological assessment data available for individuals born preterm and term and their mothers' perspective on recalled parental rearing behaviour. Participants also completed the Patient Health Questionnaire-9 (PHQ-9). Results: There were substantial similarities between reported recalled maternal rearing behaviour of individuals born preterm and at term and their mothers, with individuals born preterm with lower gestational age (age of the pregnancy from the woman's last menstrual period) recalling mothers as comparatively more controlling and overprotective. Incongruence in recalled rejection/punishment was associated with more depressive symptoms. Late first skin-to-skin contact was related to more recalled maternal rejection/punishment, less emotional warmth, and more control/overprotection. Conclusions: this study expands the knowledge about the interrelations of preterm birth, maternal rearing behaviour, and mental health, underscoring the relevance of first relationship experiences, including close intimate contact.

Impact of depersonalization on the course of depression: longitudinal observations from the gutenberg health study.

BACKGROUND: Symptoms of depersonalization (DP) and derealization (DR) are a risk factor for more severe impairment, non-response to various treatments, and a chronic course. In this study, we investigated the effects of DP/DR symptoms in patients with clinically significant depressive symptoms on clinical characteristics and various outcomes in a representative population-based sample with a 5-year follow-up. METHODS: The middle-aged sample comprised n = 10,422 persons at baseline, of whom n = 9,301 were free from depressive and DP/DR symptoms. N = 522 persons had clinically significant depression (PHQ-9 ≥ 10) and co-occurring DP/DR symptoms, and n = 599 persons had clinically significant depression (PHQ-9 ≥ 10) without DP/DR symptoms. RESULTS: There were substantial health disparities between persons with and without depression. These disparities concerned a wide range of life domains, including lower quality of the recalled early life experiences with the parents, current socioeconomic status, social integration (partnership, loneliness), current social and interpersonal stressors (family, work), functional bodily complaints (e.g., tinnitus, migraine, chest pain), unhealthy lifestyle, and the prevalence of already developed physical diseases. These disparities persisted to the 5-year follow-up and were exceptionally severe for depressed persons with co-occurring DP/DR symptoms. Among the depressed persons, the co-occurrence of DP/DR symptoms more than doubled the risk for recurrence or persistence of depression. Only 6.9% of depressed persons with DP/DR symptoms achieved remission at the 5-year follow-up (PHQ-9 < 5). Depression with and without co-occurring DP/DR worsened self-rated physical health significantly. The impact of depression with co-occurring DP/DR on the worsening of the self-rated physical health status was stronger than those of age and major medical diseases (e.g., heart failure). However, only depression without DP/DR was associated with mortality in a hazard regression analysis adjusted for age, sex, and lifestyle. CONCLUSIONS: The results demonstrated that DP/DR symptoms represent an important and easily assessable prognostic factor for the course of depression and health outcomes. Given the low remission rates for depression in general and depression with DP/DR in particular, efforts should be made to identify and better support this group, which is disadvantaged in many aspects of life.

Redox mechanisms in autoimmune thyroid eye disease.

Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1ß, IL-6, and transforming growth factor (TGF)-ß. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.

Macular Curvature in Adults Born Preterm With and Without ROP: Results from the Gutenberg Prematurity Eye Study.

Purpose: This study investigated the effects of prematurity and retinopathy of prematurity (ROP) as well as the associations of the ocular geometry with macular curvature in adults. Methods: The Gutenberg Prematurity Eye Study is a retrospective cohort study of preterm and full-term participants aged 18 to 52 years with a prospective ophthalmologic examination. The main outcome measure was the macular curvature in the central foveal optical coherence tomography (OCT) scan and its associations with gestational age (GA), birth weight and birth weight percentile, ROP occurrence, ROP treatment, and other perinatal factors were evaluated in univariable and multivariable linear regression analyses. Furthermore, a second model assessed the association of ocular geometry with macular curvature. Results: In the present study, 550 eyes of 284 adults born preterm and 277 eyes of 139 adults born full-term were examined (aged = 28.7 ± 8.7 years, 240 female subjects). In multivariable analyses for perinatal parameters, ROP treatment (B = -52.44, P = 0.023) and maternal smoking during pregnancy (B = 26.41, P = 0.019) showed an association with macular curvature. Regarding ocular geometric parameters, posterior segment length (B = 9.07, P < 0.001) and subfoveal choroidal thickness (B = -0.26, P < 0.001) were associated with macular curvature, central corneal thickness, anterior chamber depth, lens thickness, and foveal retinal thickness were not associated. Conclusions: Adults treated for ROP had relatively more negative curvature values compared to the full-term group, indicating a macular protrusion toward the vitreous cave. A thicker subfoveal choroidal thickness was associated with a flatter macular curvature, whereas a longer posterior segment length was associated with a steeper macular curvature indicating the characteristics of the myopic elongation of the eye.

Bi-Gaussian analysis reveals distinct education-related alterations in spherical equivalent and axial length-results from the Gutenberg Health Study.

PURPOSE: The aim of this study is to investigate the distribution of spherical equivalent and axial length in the general population and to analyze the influence of education on spherical equivalent with a focus on ocular biometric parameters. METHODS: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany. Participants underwent comprehensive ophthalmologic examinations as part of the 5-year follow-up examination in 2012-2017 including genotyping. The spherical equivalent and axial length distributions were modeled with gaussian mixture models. Regression analysis (on person-individual level) was performed to analyze associations between biometric parameters and educational factors. Mendelian randomization analysis explored the causal effect between spherical equivalent, axial length, and education. Additionally, effect mediation analysis examined the link between spherical equivalent and education. RESULTS: A total of 8532 study participants were included (median age: 57 years, 49% female). The distribution of spherical equivalent and axial length follows a bi-Gaussian function, partially explained by the length of education (i.e., < 11 years education vs. 11-20 years). Mendelian randomization indicated an effect of education on refractive error using a genetic risk score of education as an instrument variable (- 0.35 diopters per SD increase in the instrument, 95% CI, - 0.64-0.05, p = 0.02) and an effect of education on axial length (0.63 mm per SD increase in the instrument, 95% CI, 0.22-1.04, p = 0.003). Spherical equivalent, axial length and anterior chamber depth were associated with length of education in regression analyses. Mediation analysis revealed that the association between spherical equivalent and education is mainly driven (70%) by alteration in axial length. CONCLUSIONS: The distribution of axial length and spherical equivalent is represented by subgroups of the population (bi-Gaussian). This distribution can be partially explained by length of education. The impact of education on spherical equivalent is mainly driven by alteration in axial length.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Prevalence of strabismus and risk factors in adults born preterm with and without retinopathy of prematurity: results from the Gutenberg Prematurity Eye study.

AIM: The purpose of this study was to assess the prevalence of strabismus and nystagmus and to analyse associated factors in preterm and full-term infants in adulthood. METHODS: The Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmological examination of participants born preterm and full-term (aged 18-52 years). Perinatal data were carefully assessed for risk factors and comprehensive ophthalmological examinations were conducted. The association between strabismus and nystagmus was assessed by analysing 16 different perinatal and actual risk factors in multivariable analysis. Participants were grouped into full-term controls (gestational age (GA) at birth ≥37 weeks), preterm participants without retinopathy of prematurity (ROP) and GA 33-36 weeks (group 2), GA 29-32 weeks (group 3), GA ≤28 weeks (group 4), non-treated ROP (group 5) and treated ROP (group 6). RESULTS: In total, 892 eyes of 450 preterm and full-term individuals (mean age: 28.6 years, SD: ± 8.6 years, 251 females) were included. Strabismus was observed in 2.1% (3/140), 6.6% (9/137), 17.4% (16/92), 11.1% (2/18), 27.1% (13/48) and 60% (9/15) of participants and nystagmus in 0.7% (1/140), 1.5% (2/137), 4.3% (4/92), 5.6% (1/18), 10.4% (5/48) and 26.7% (4/15) of participants in the respective groups. In the multivariable regression model, strabismus was associated with GA (OR=0.90; p=0.046), anisometropia ≥1.5 diopter (OR=3.87; p=0.003), hypermetropia ≥2 diopter (OR=9.89; p<0.001) and astigmatism ≥1.5 diopter (OR=2.73; p=0.017). Esotropia was more frequent than exotropia and hypermetropia/hypometropia. Most strabismus cases occurred within the first 10 years of life. The strongest predictor associated with nystagmus was perinatal adverse events (OR=15.8; p=0.002). CONCLUSION: Low GA and refraction of the eye are independent risk factors for strabismus, which typically occurs in the first 10 years of life. Perinatal adverse events are the most important factors for the presence of nystagmus in adulthood.