Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery.

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.

Vaccines and the Eye: Current Understanding of the Molecular and Immunological Effects of Vaccination on the Eye.

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

[OPHTHALMOLOGY - ON THE TIP OF THE SPEAR].

INTRODUCTION: Ophthalmology is a broad branch of medicine, which includes an extensive range of sub-specialties on one hand, and interfaces with other fields of medicine on the other. This issue contains papers from different sub-specialties of ophthalmology, that together cover several of the most important issues in this field. These papers present the topics in a manner compatible with the wide readership of the journal, and touch upon the most current updates and innovations. The original articles in this issue deal with treatments for the prevention of myopia progression in children, treatment of complicated cases of retinal detachment in children, ocular manifestations of vascular abnormalities in patients with coronavirus, and a series of patients with corneal damage due to ultraviolet-C (UVC) lamps intended to clear the air of this virus. The review papers describe glaucoma and the current change in its treatment paradigm, which focuses on earlier intervention, ocular manifestations of systemic autoimmune diseases, and the possibilities for artificial corneal implantation. We hope that this special issue will be of interest and clinical value to its readers.

[Structure of pediatric ophthalmic pathology in Uzbekistan]. / Struktura detskoi oftal'mopatologii v Uzbekistane.

PURPOSE: This study analyzes the structure of eye diseases in children of different age groups based on the materials of the ophthalmology department of the Tashkent Pediatric Medical Institute (TPMI) clinic for 2018-2021. MATERIAL AND METHODS: A retrospective analysis of statistical coupons was conducted, which included the medical records of 5613 patients of the ophthalmology department of the TPMI clinic. RESULTS: In the age structure of ophthalmopathology in children who received inpatient treatment at the TPMI clinic in 2018-2021, children aged 5 to 14 years (49.5%) and 1 to 5 years (30.7%) were significantly predominant. The proportion of patients under 1 year old was 11.2% and from 14 to 18 years old - 7.5%. Congenital glaucoma (41%) and lens diseases (30.4%) are characteristic of infants (from 0 to 1 year old); in patients aged 1 to 5 years, lens pathology (37%), congenital glaucoma (25.2%), and injuries (24.7%) were more common; in children aged 5 to 14 years, the pathology of the oculomotor apparatus (32%) and injuries (27.7%) prevailed; in the age group from 14 to 18 years, lens diseases (28.4%) and injuries of the organ of vision (28.1%) were detected more often. CONCLUSIONS: The revealed age aspects of nosologies are due to the timing of clinical manifestations of the pathology, late seeking ophthalmic care of parents, presence of a concomitant pathology in the child, which prevents surgical treatment. The results of the study will help optimize planned and emergency ophthalmological care for children in the regions of the republic.

Obesity, body fat distribution and eye diseases.

BACKGROUND: The prevalence of obesity, a chronic disease, is increasing, and obesity is now considered a global epidemic. Eye diseases are also increasing worldwide and have serious repercussions on quality of life as well as increasingly high costs for the community. The relationships between obesity and ocular pathologies are not yet well clarified and are not pathologically homogeneous: they seem to be somehow linked to excess body fat, especially to the distribution of adipose tissue and its ectopic deposits. PURPOSE: Our objective was to examine the associations between obesity and anthropometric indices, including body mass index (BMI), waist circumference (WC), and the waist/hip ratio (WHR), and the risk of most widespread eye diseases, with particular attention given to the most significant metabolic mechanisms. METHODS: This article provides a narrative overview of the effect of obesity and anthropometric measurements of body fat on prevalent eye diseases. We used the MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library databases from 1984 to 2024. In addition, we hand-searched references from the retrieved articles and explored a number of related websites. A total of 153 publications were considered. RESULTS: There is significant evidence that obesity is associated with several eye diseases. Waist circumference (WC) and the waist/hip ratio (WHR) have been observed to have stronger positive associations with eye diseases than BMI. CONCLUSIONS: Obesity must be considered a significant risk factor for eye diseases; hence, a multidisciplinary and multidimensional approach to treating obesity, which also affects ocular health, is important. In the prevention and treatment of eye diseases related to obesity, lifestyle factors, especially diet and physical activity, as well as weight changes, both weight loss and weight gain, should not be overlooked. LEVEL OF EVIDENCE: Level V narrative review.

Barriers to uptake of referral services from secondary eye care to tertiary eye care and its associated determinants in L V Prasad Eye Institute network in Southern India: A cross-sectional study-Report II.

AIM: To investigate the barriers to the uptake of referral services from secondary care centers (SC) to a higher-level tertiary care center (TC) in Southern India. METHODS: A cross-sectional study was conducted in the Mahabubnagar district of Telangana, India, between February 1, 2018 to January 31, 2019 and all those referred from SC to TC between January 1, 2013 to December 30, 2016 were identified for interview. Based on inclusion criteria, of the 960 participants identified, 681 (70.9%) participated in the study. A validated study questionnaire was administered to all participants. Information collected were the demographic details, details related to their referral and barriers to referral. The participants that presented at TC were considered compliant and who did not, were non-compliant. Reasons for non-compliance was also collected. RESULTS: The mean age those interviewed was 46.1 years (SD: 17.3 years) and 429 (63%) were males and 252 (37%) were females. Overall, 516 (75.8%) were compliant, and 165 (24.2%) were non-compliant. The major factors for non-compliance were economic (16.4%) and attitudinal (44.2%) barriers. Within the attitudinal barrier category, the most prevalent individual attitudinal barriers were 'too busy to go to the eye center for treatment (16.4%)'and 'able to manage routine daily activities with current vision (12.1%)'. The multivariable analysis showed that the non-compliant participants had only visited the SC once prior to the referral (odds ratio: 2.82; 95% CI: 1.43-5.57) (p = 0.003). CONCLUSIONS: Participants with only one SC visit, were less likely to comply with referrals and the major barriers to compliance were economical and attitudinal. It is important to address these specific barriers to provide proper counseling to participants during referrals.

Imaging performance of portable and conventional ultrasound imaging technologies for ophthalmic applications.

PURPOSE: The aim of this study was to evaluate the imaging capabilities of Butterfly iQ with conventional ophthalmic (piezoelectric) ultrasound (COU) for ophthalmic imaging. METHODS: Custom phantom molds were designed and imaged with Butterfly iQ and COU to compare spatial resolution capabilities. To evaluate the clinical imaging performance of Butterfly iQ and COU, a survey containing pathological conditions from human subjects, imaged with both Butterfly iQ and COU probes, was given to three retina specialists and graded on image detail, resolution, quality, and diagnostic confidence on a ten-point Likert scale. Kruskal-Wallis analysis was performed for survey responses. RESULTS: Butterfly iQ and COU had comparable capabilities for imaging small axial and lateral phantom features (down to 0.1 mm) of high and low acoustic reflectivity. One of three retina specialists demonstrated a statistically significant preference for COU related to resolution, detail, and diagnostic confidence, but the remaining graders showed no significant preference for Butterfly iQ or COU across all sample images presented. CONCLUSION: The emergence of portable ultrasound probes offers an affordable alternative to COU technologies with comparable qualitative imaging resolution down to 0.1 mm. These findings suggest the value to further study the use of portable ultrasound systems and their utility in routine eye care.

The association of symptomatic vitreous floaters with depression and anxiety.

PURPOSE: To evaluate the levels of anxiety and depression in patients with symptomatic vitreous floaters and to determine the possible correlations of psychological implications with the symptoms duration and possible improvement, the degree of posterior vitreous detachment, and the discomfort severity. METHODS: Ninety patients complaining for floaters and fifty-seven age- and gender-matched healthy-control subjects were recruited. Every participant underwent a complete ophthalmological examination, including funduscopy and optical coherence tomography scans, while clinical and demographic data were also gathered. The Patient Health Questionnaire-9 (PHQ-9), the Zung Depression Inventory-Self-Rating Depression Scale (Zung SDS), and the Hospital Anxiety and Depression Scale (HADS) were completed by everyone. RESULTS: Between the studied groups, no significant differences were detected regarding the clinical and demographic data (p > 0.05). The patients with floaters had significantly higher scores of PHQ-9, Zung SDS, HADS Anxiety, and HADS Depression (p < 0.001). After adjustment for several confounders, PHQ-9 (p = 0.041), Zung SDS (p = 0.003), and HADS Anxiety (p = 0.036) values remained significantly impaired. Among the patients, PHQ-9 and Zung SDS scores were significantly elevated in the patients with floaters duration less than 4 weeks (p < 0.05). Finally, anxiety and depression were significantly correlated with the symptoms duration and intensity, with the floater-associated discomfort, and with the stage of posterior vitreous detachment. CONCLUSION: Vitreous floaters have a negative impact on patients' psychological status, by the terms of enhanced depressive and anxiety levels. To the best of our knowledge, our study is the first in the literature to elaborate the aforementioned association, by assessing three different questionnaires simultaneously.

Light Scattering by Vitreous of Humans With Vision Degrading Myodesopsia From Floaters.

Purpose: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL. Methods: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission in vitro. Results: All indices of vitreous echodensity in vivo correlated positively with straylight at 0.5° (R = 0.708 to 0.775, P = 0.049 and 0.024, respectively). Straylight mean scatter index correlated with echodensity (R = 0.71, P = 0.04) and VQOL (R = -0.82, P = 0.0075). Dark-field measures in vitro correlated with degraded CS in vivo (R = -0.69, P = 0.04). VQOL correlated with straylight mean scatter index (R = -0.823, P = 0.012). Conclusions: Increased vitreous echodensity in vivo is associated with more straylight scattering in vitro, validating ultrasonography as a clinical surrogate for light scattering. Contrast sensitivity in vivo is more degraded in the presence of dark-field scattering in vitro and VQOL is decreased in patients whose vitreous has increased light scattering. These findings could form the basis for the development of optical corrections for VDM or support new laser treatments, as well as novel pharmacotherapy.

Ocular lesions in patients with ulcerative colitis.

OBJECTIVE: Aim: To analyze the data and evaluate the prevalence of ocular lesions in patients with moderate ulcerative colitis. PATIENTS AND METHODS: Materials and Methods: We observed 112 patients aged 18-75 years old with clinically, endoscopically and histologically confirmed moderate ulcerative colitis which lasted at least 6 months. An ophthalmologic exam was performed to determine the presence of ocular symptoms. RESULTS: Results: Of the 112 patients with moderate ulcerative colitis, 21 (18,75%) had the following ocular lesions: episcleritis - 7 patients (6,25%), keratopathy - 5 patients (4,46%), uveitis - 5 patients (4,46%), cataract - 2 (1,78%) and scleritis - 2 (1.78%). CONCLUSION: Conclusions: Because ocular symptoms in patients with UC are often nonspecific, it may be beneficial to perform ophthalmologic examinations as a routine follow-up component of in such patients.

An overview of neuro-ophthalmic disorders at Jenna Ophthalmic Center, Baghdad, Iraq (2021-2022).

Neuro-ophthalmic disorders are often documented individually for each illness, with little data available on their overall incidence and pattern. The overall incidence of neuro-ophthalmic illnesses in Iraq is still not recorded. This study aimed to evaluate the clinical, demographic, and etiological features of patients seeking consultation at an Iraqi neuro-ophthalmology clinic. A prospective cross-sectional observational research was conducted at the Janna Ophthalmic Center in Baghdad, Iraq. The center serves a diverse patient population from various governorates. All newly diagnosed patients with neuro-ophthalmic disorders who visited the neuro-ophthalmological clinic, regardless of gender or age group, were included. The neuro-ophthalmologist established a diagnosis for each case by reviewing the patient's medical history, doing physical examinations, administering specific tests, and, in certain cases, using neuroimaging methods. The duration of the study was extended from March 2021 to November 2022. Among the 6440 patients evaluated, 613 cases were confirmed at the neuro-ophthalmology clinic. Ischemic optic neuropathy (NAION, AION, and PION) was the most prevalent diagnosis, accounting for 17.61% of newly reported cases in the field of neuro-ophthalmology. This was followed by sixth nerve palsy. Diabetes mellitus affected 42.7% of the cases, followed by hypertension, which affected 39.3% of the participants. The incidence of neuro-ophthalmic diseases tended to be high. Ischemic optic neuropathy and sixth nerve palsy, traumatic/compressive optic neuropathy, and papilledema were the most common neuro-ophthalmic disorders reported.

Myopia and Nutrient Associations with Age-Related Eye Diseases in Korean Adults: A Cross-Sectional KNHANES Study.

This study assessed the prevalence of myopia, cataracts, glaucoma, and macular degeneration among Koreans over 40, utilizing data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2018). We analyzed 204,973 adults (44% men, 56% women; mean age 58.70 ± 10.75 years), exploring the association between myopia and these eye diseases through multivariate logistic regression, adjusting for confounders and calculating adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results showed a myopia prevalence of 44.6%, cataracts at 19.4%, macular degeneration at 16.2%, and glaucoma at 2.3%, with significant differences across ages and genders. A potential link was found between myopia and an increased risk of cataracts and macular degeneration, but not with glaucoma. Additionally, a higher dietary intake of carbohydrates, polyunsaturated and n-6 fatty acids, vitamins, and minerals correlated with lower risks of these diseases, underscoring the importance of the diet in managing and preventing age-related eye conditions. These findings highlight the need for dietary considerations in public health strategies and confirm myopia as a significant risk factor for specific eye diseases in the aging Korean population.

The Hippo signalling pathway and its impact on eye diseases.

The Hippo signalling pathway, an evolutionarily conserved kinase cascade, has been shown to be crucial for cell fate determination, homeostasis and tissue regeneration. Recent experimental and clinical studies have demonstrated that the Hippo signalling pathway is involved in the pathophysiology of ocular diseases. This article provides the first systematic review of studies on the regulatory and functional roles of mammalian Hippo signalling systems in eye diseases. More comprehensive studies on this pathway are required for a better understanding of the pathophysiology of eye diseases and the development of effective therapies.

Hemoglobin levels are associated with retinal vascular caliber in a middle-aged birth cohort.

Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (Bmales = 0.068 [0.001; 0.135], Bfemales = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases.

"Spaceflight-to-Eye Clinic": Terrestrial advances in ophthalmic healthcare delivery from space-based innovations.

The phrase "Bench-to-Bedside" is a well-known phrase in medicine, highlighting scientific discoveries that directly translate to impacting patient care. Key examples of translational research include identification of key molecular targets in diseases and development of diagnostic laboratory tests for earlier disease detection. Bridging these scientific advances to the bedside/clinic has played a meaningful impact in numerous patient lives. The spaceflight environment poses a unique opportunity to also make this impact; the nature of harsh extraterrestrial conditions and medically austere and remote environments push for cutting-edge technology innovation. Many of these novel technologies built for the spaceflight environment also have numerous benefits for human health on Earth. In this manuscript, we focus on "Spaceflight-to-Eye Clinic" and discuss technologies built for the spaceflight environment that eventually helped to optimize ophthalmic health on Earth (e.g., LADAR for satellite docking now utilized in eye-tracking technology for LASIK). We also discuss current technology research for spaceflight associated neuro-ocular syndrome (SANS) that may also be applied to terrestrial ophthalmic health. Ultimately, various advances made to enable to the future of space exploration have also advanced the ophthalmic health of individuals on Earth.

Microfluidic Fabricated Liposomes for Nutlin-3a Ocular Delivery as Potential Candidate for Proliferative Vitreoretinal Diseases Treatment.

Purpose: Proliferative vitreoretinal diseases (PVDs) represent a heterogeneous group of pathologies characterized by the presence of retinal proliferative membranes, in whose development retinal pigment epithelium (RPE) is deeply involved. As the only effective treatment for PVDs at present is surgery, we aimed to investigate the potential therapeutic activity of Nutlin-3a, a small non-genotoxic inhibitor of the MDM2/p53 interaction, on ARPE-19 cell line and on human RPE primary cells, as in vitro models of RPE and, more importantly, to formulate and evaluate Nutlin-3a loaded liposomes designed for ophthalmic administration. Methods: Liposomes were produced using an innovative approach by a microfluidic device under selection of different conditions. Liposome size distribution was evaluated by photon correlation spectroscopy and centrifugal field flow fractionation, while the liposome structure was studied by transmission electron microscopy and Fourier-transform infrared spectroscopy. The Nutlin-3a entrapment capacity was evaluated by ultrafiltration and HPLC. Nutlin-3a biological effectiveness as a solution or loaded in liposomes was evaluated by viability, proliferation, apoptosis and migration assays and by morphological analysis. Results: The microfluidic formulative study enabled the selection of liposomes composed of phosphatidylcholine (PC) 5.4 or 8.2 mg/mL and 10% ethanol, characterized by roundish vesicular structures with 150-250 nm mean diameters. Particularly, liposomes based on the lower PC concentration were characterized by higher stability. Nutlin-3a was effectively encapsulated in liposomes and was able to induce a significant reduction of viability and migration in RPE cell models. Conclusion: Our results lay the basis for a possible use of liposomes for the ocular delivery of Nutlin-3a.

Susceptibility of optic nerve head in children with posture-related elevation of intraocular pressure.

BACKGROUND/AIMS: This work aimed to investigate changes in optic nerve head (ONH) morphometry based on Bruch membrane opening in children with extensive nocturnal intraocular pressure (IOP) elevations. METHODS: The course of Bruch membrane opening-based optic nerve head (ONH) morphometry was analysed in thirty-two patients younger than 18 years with evaluable SD-OCT examinations of the ONH and nocturnal posture-dependent IOP elevation above 25 mmHg. Longitudinal changes in neuroretinal rim tissue, as measured by Bruch Membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness, were assessed. RESULTS: One year after the 24 h IOP measurement, global BMO-MRW (- 1.61 ± 16.8 µm, n.s.; p = 0.611) and RNFL (+ 0.64 ± 3.17 µm; n.s.; p = 0.292) measurements were not significantly different from the baseline. No significant BMO-MRW reduction (- 3.91 ± 24.3 µm; n.s. p = 0.458) or deviation in RNFL thickness (+ 1.10 ± 3.52 µm) was observed at the four-year follow-up. Absolute IOP values measured in the supine position did not correlate with changes in global BMO-MRW or RNFL thickness. CONCLUSION: Posture-dependent IOP elevations do not seem to influence retinal nerve fibre layer thickness or Bruch membrane opening-based morphometric data in childhood.