Views and opinions of patients with glaucoma and age-related macular degeneration on vision home-monitoring: a UK-based focus group study.

OBJECTIVE: To investigate the views, hopes and concerns of patients living with glaucoma and age-related macular degeneration (AMD) regarding vision home-monitoring. DESIGN: Qualitative study using focus groups and questionnaires. Participants were given three disease-relevant home-monitoring tests to try. The tests consisted of three visual field tests for the glaucoma groups (Melbourne Rapid Fields, Eyecatcher, Visual Fields Fast) and three acuity and/or contrast-sensitivity tests for AMD groups (Alleye, PopCSF, SpotChecks). Focus group data were thematically analysed. SETTING: University meeting rooms in London, UK. PARTICIPANTS: Eight people with glaucoma (five women, median age 74) and seven people with AMD (four women, median age 77) volunteered through two UK-based charities. Participants were excluded if they did not self-report a diagnosis of glaucoma or AMD or if they lived further than a 1-hour travel distance from the university (to ensure minimal travel burden on participants). RESULTS: Six themes emerged from focus groups, the two most frequently referenced being: 'concerns about home-monitoring' and 'patient and practitioner access to results'. Overall, participants believed home-monitoring could provide patients with a greater sense of control, but also expressed concerns, including: the possibility of home-monitoring replacing face-to-face appointments; the burden placed on clinicians by the need to process additional data; struggles to keep up with requisite technologies; and potential anxiety from seeing worrying results. Most devices were scored highly for usability, though several practical improvements were suggested. CONCLUSION: Patients with mild-to-moderate glaucoma/AMD expect vision home-monitoring to be beneficial, but have significant concerns about its potential implementation.

Evolutionary conservation of VSX2 super-enhancer modules in retinal development.

Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. We recently identified developmental stage- and cell type-specific modules within the murine Vsx2 SE. Here, we show that the human VSX2 SE modules have similar developmental stage- and cell type-specific activity in reporter gene assays. By inserting the human sequence of one VSX2 SE module into a mouse with microphthalmia, eye size was rescued. To understand the function of these SE modules during human retinal development, we deleted individual modules in human embryonic stem cells and generated retinal organoids. Deleting one module results in small organoids, recapitulating the small-eyed phenotype of mice with microphthalmia, while deletion of the other module led to disruptions in bipolar neuron development. This prototypical SE serves as a model for understanding developmental stage- and cell type-specific effects of neurogenic transcription factors with complex expression patterns. Moreover, by elucidating the gene regulatory mechanisms, we can begin to examine how dysregulation of these mechanisms contributes to phenotypic diversity and disease.

Non-syndromic OTX2-associated pattern dystrophy: a 10-year multimodal imaging study.

PURPOSE: To report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy. METHODS: A 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)]. RESULTS: Visual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction. CONCLUSIONS: This case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted.

Fluorescein Angiogram Causing Cutaneous Venous Staining: A Rare Self-Resolving Phenomenon.

Introduction: Fluorescein angiography (FA) is a useful investigation in the diagnosis and treatment of retinal and choroidal disease. FA has well-reported adverse effects, most being mild. Very few cases have reported cutaneous venous staining following FA. Case Presentation: Two cases are reported. Case 1 was a 90-year-old female with bilateral neovascular age-related macular degeneration. In the few minutes following her routine FA, she developed cutaneous fluorescein staining ascending along the superficial forearm veins proximal to the cannula in situ at the dorsal wrist. Case 2 was a 50-year-old male with diabetic macular oedema. In the minutes following his FA, he developed cutaneous fluorescein staining descending along the dorsal forearm veins distal to the cannula in situ at the cubital fossa. Both patients were managed conservatively with the stain resolving in the next few days. Conclusion: Cutaneous fluorescein staining around superficial vasculature is a rare phenomenon. Despite this, it seems to be self-limiting and does not require any treatment.

Microglia depletion leads to increased susceptibility to ocular hypertension-dependent glaucoma.

In recent years, microglia have been highlighted for playing integral roles in neurodegenerative diseases, like glaucoma. To better understand the role of microglia during chronic ocular hypertension, we depleted microglia from aged (9-12 months old) DBA/2 J (D2) mice, which exhibit age-related increases in intraocular pressure, using a dietary CSF1R antagonist, PLX5622. Retinal ganglion cell (RGC) somas were counted, and optic nerve cross-sections stained and assessed for glaucomatous damage. Sustained administration of dietary PLX5622 significantly reduced the numbers of retinal microglia. Dietary PLX5622 did not lead to changes in intraocular pressure in D2 or normotensive DBA/2 J-Gpnmb+ (D2-Gpnmb+ ) control mice. While PLX5622-treated D2-Gpnmb+ did not develop optic nerve damage, PLX5622-treated D2 mice showed a significant increase in moderate-to-severe optic nerve damage compared to D2 mice fed a control diet. In conclusion, global reduction of microglia exacerbated glaucomatous neurodegeneration in D2 mice suggesting microglia play an overall beneficial role in protecting from ocular hypertension associated RGC loss.

Large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration.

Many genes are known to regulate retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited cell loss, per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 101 genes identified seven knockouts that inhibited and eleven that promoted RGC regeneration. Surprisingly, 35 of 36 genes known/implicated as being required for regeneration following widespread retinal damage were not required for RGC regeneration, and seven even enhanced regeneration kinetics, including proneural factors neurog1, olig2, and ascl1a. Mechanistic analyses revealed ascl1a disruption increased the propensity of progenitor cells to produce RGCs; i.e., increased "fate bias". These data demonstrate plasticity in how Müller glia can convert to a stem-like state and context-specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.

Cone photoreceptor differentiation regulated by thyroid hormone transporter MCT8 in the retinal pigment epithelium.

The key role of a thyroid hormone receptor in determining the maturation and diversity of cone photoreceptors reflects a profound influence of endocrine signaling on the cells that mediate color vision. However, the route by which hormone reaches cones remains enigmatic as cones reside in the retinal photoreceptor layer, shielded by the blood-retina barrier. Using genetic approaches, we report that cone differentiation is regulated by a membrane transporter for thyroid hormone, MCT8 (SLC16A2), in the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier. Mct8-deficient mice display hypothyroid-like cone gene expression and compromised electroretinogram responses. Mammalian color vision is typically facilitated by cone types that detect medium-long (M) and short (S) wavelengths of light but Mct8-deficient mice have a partial shift of M to S cone identity, resembling the phenotype of thyroid hormone receptor deficiency. RPE-specific ablation of Mct8 results in similar shifts in cone identity and hypothyroid-like gene expression whereas reexpression of MCT8 in the RPE in Mct8-deficient mice partly restores M cone identity, consistent with paracrine-like control of thyroid hormone signaling by the RPE. Our findings suggest that in addition to transport of essential solutes and homeostatic support for photoreceptors, the RPE regulates the thyroid hormone signal that promotes cone-mediated vision.

Insulin resistance in the retina: possible implications for certain ocular diseases.

Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.

An Analysis of Optic Disc Parameters in Patients with Peripheral Retinal Tears Following Acute Posterior Vitreous Detachment: A Cross-Sectional Study.

Background: To investigate association between optic disc parameters analyzed by optical coherence tomography (OCT) and occurrence of peripheral retinal tears in patients with symptomatic posterior vitreous detachment (PVD). Methods: This cross-sectional study enrolled 75 patients with symptoms of acute PVD, who were allocated into two groups based on whether a peripheral retinal tear occurred or not. Results: When comparing the average retinal nerve fiber layer (RNFL) thickness (µm) between retinal tear and control groups, it was shown that patients with a retinal tear have a significantly higher (87.18 [95% confidence interval (CI), 84.47 to 89.9] vs 81.14 [95% CI, 77.81 to 84.46], P = 0.005) average RNFL thickness. Furthermore, we observed a significant difference (0.13, 0.06 to 0.22 vs 0.07, 0.04 to 0.1, P = 0.036, Mann-Whitney U-test) in the size of cup volume (mm3) between the tear and control groups, respectively. Linear regression showed a significant decrease (P = 0.029) in average RNFL thickness with increasing age, but without a significant difference between the two groups. There was no statistically significant difference between the tear and control groups in terms of rim area, disc area, and average cup-to-disc ratio. Conclusion: Patients with a higher average RNFL thickness and larger cup volume measured by OCT were more prone to develop a peripheral retinal tear. Increased peripapillary average RNFL thickness due to trauma and subsequent inflammation, possibly related to the more adherent posterior hyaloid membrane to the retina, may also indicate strengthened adhesions in the areas of the peripheral retina where retinal tears occur. OCT analysis of the optic nerve head may be used in everyday clinical practice as a predictor of the development of peripheral retinal tears in patients with symptomatic PVD.

Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy.

Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the well-known anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and in vitro models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different in vitro models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively), was able to significantly reduce (p < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly (p < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose vs . axitinib 1 µM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action.

The intracellular domain of Sema6A is essential for development of the zebrafish retina.

Semaphorin6A (Sema6A) is a repulsive guidance molecule that plays many roles in central nervous system, heart, and bone development, as well as immune system responses and cell signaling in cancer. Loss of Sema6A or its receptor PlexinA2 in zebrafish leads to smaller eyes and improper retinal patterning. Here we investigate a potential role for the Sema6A intracellular domain in zebrafish eye development and dissect which phenotypes rely on forward signaling and which rely on reverse signaling. We performed rescue experiments on zebrafish Sema6A morphants with either full-length Sema6A (Sema6A-FL) or Sema6A lacking its intracellular domain (Sema6A-ΔC). We identified that the intracellular domain is not required for eye size and retinal patterning, however it is required for retinal integrity, the number and end feet strength of Müller glia and protecting against retinal cell death. This novel function for the intracellular domain suggests a role for Sema6A reverse signaling in zebrafish eye development.

Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis.

Background: The concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship. Methods: The genome-wide association study's (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn's disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio. Results: The causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835-0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837-0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828-0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801-0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865-0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841-0.924; P value= 1.82E-07) could reduce the risk of CD. What's more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873-0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861-0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships. Conclusions: Our research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.

RETINAL AND VITREOUS CHANGES ASSOCIATED WITH SPONTANEOUS IMPROVEMENT IN MYOPIC MACULAR SCHISIS.

PURPOSE: To describe the retinal and vitreous changes in eyes showing myopic macular schisis (MMS) improvement when vitrectomy was not performed and identify triggering factors. DESIGN: Retrospective observational study. SUBJECTS: Patients with non-operated myopic macular schisis METHODS: The records of patients with MMS who were followed without performing surgery for more than 6 months were retrospectively reviewed, and the eyes showing an anatomical improvement were included. MMS evolution was analyzed quantitatively (central foveal thickness [CFT], parafoveal thickness, maximum height) and qualitatively (presence/absence of foveal detachment, lamellar hole, epiretinal membrane, choroidal neovascularization, inner and outer retinoschisis, vitreous status) at baseline and at the final visit. An anatomical improvement was defined as a decrease in CFT by at least 50 µm. MAIN OUTCOME MEASURE: The rate anatomical improvement of MMS without performing vitrectomy and the morphological changes observed in these cases. RESULTS: In a cohort of 74 non-operated eyes with MMS, MMS improved in 14 eyes (19%) after a mean follow-up of 55 ± 38 months (range: 8-138). In these improved cases, the mean decrease in CFT was 153 ± 166 µm (range: 24-635, p=0.005) and a complete resolution of MMS was observed in 9 eyes (64%). In 9 eyes (64%), the improvement was associated with visible vitreous changes in the macular area on the OCT scans. The mean visual acuity, which was already good at baseline (20/50, 0.4 ± 0.2 LogMAR), increased at the last visit (20/40, 0.3 ± 0.3 LogMAR) but without reaching significance. CONCLUSION: This long-term follow-up analysis showed that almost 20% of MMS in eyes without indication for surgery could improve over time. In most cases, the improvement was associated with an apparent resolution of vitreous tensions.

Short-term effects of sunlight exposure on fundus blood flow perfusion in children: a randomised controlled trial.

AIM: To evaluate the short-term effects of different sunlight exposure on fundus blood flow perfusion (BFP) after near work. METHODS: In this parallel randomised controlled trial, 81 students aged 7-15 with spherical equivalent refraction between -2.00 and +3.00 diopters were randomly assigned to either a low-illuminance (4k lux) group (N=40) or high-illuminance (10k lux) (N=41). Following 1 hour indoor reading, participants had sunlight exposure matching their group's intensity for 15 minutes. BFPs in the superficial retina, deep retina and choroid were measured at four time points: pre-reading, post-reading, 5th-minute and 15th-minute sunlight exposure. RESULTS: Within the initial 5 minutes of sunlight exposure, the 10k lux group showed a tendency for decreased BFP, particularly in the choroid (superficial retina: -0.2, 95% CI -0.9 to 0.5; deep retina: -0.1, 95% CI -0.6 to 0.4; choroid: -0.4, 95% CI -0.8 to 0.0), while the 4k lux group exhibited an increase (superficial retina: 0.7, 95% CI 0.1 to 1.3; deep retina: 0.3, 95% CI -0.2 to 0.8; choroid: 0.1, 95% CI -0.2 to 0.5). From 5 to 15 minutes, BFP decreased in both groups. At the 5th-minute mark, the 10k lux group exhibited a greater decrease in choroid (10k -0.4 vs 4k 0.1, p=0.051). No significant difference was observed after 15 minutes of exposure. CONCLUSION: Higher illuminance sunlight exposure can restore fundus BFP more rapidly than lower; however, duration remains pivotal. To prevent myopia, continuous sunlight exposure for over 15 minutes is recommended to aid in reinstating the fundus BFP increased by near work. TRIAL REGISTRATION NUMBER: NCT05594732.

Multimodal in-vivo maps as a tool to characterize retinal structural biomarkers for progression in adult-onset Stargardt disease.

Purpose: To characterize retinal structural biomarkers for progression in adult-onset Stargardt disease from multimodal retinal imaging in-vivo maps. Methods: Seven adult patients (29-69 years; 3 males) with genetically-confirmed and clinically diagnosed adult-onset Stargardt disease and age-matched healthy controls were imaged with confocal and non-confocal Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO), optical coherence tomography (OCT), fundus infrared (FIR), short wavelength-autofluorescence (FAF) and color fundus photography (CFP). Images from each modality were scaled for differences in lateral magnification before montages of AOSLO images were aligned with en-face FIR, FAF and OCT scans to explore changes in retinal structure across imaging modalities. Photoreceptors, retinal pigment epithelium (RPE) cells, flecks, and other retinal alterations in macular regions were identified, delineated, and correlated across imaging modalities. Retinal layer-thicknesses were extracted from segmented OCT images in areas of normal appearance on clinical imaging and intact outer retinal structure on OCT. Eccentricity dependency in cell density was compared with retinal thickness and outer retinal layer thickness, evaluated across patients, and compared with data from healthy controls. Results: In patients with Stargardt disease, alterations in retinal structure were visible in different image modalities depending on layer location and structural properties. The patients had highly variable foveal structure, associated with equally variable visual acuity (-0.02 to 0.98 logMAR). Cone and rod photoreceptors, as well as RPE-like structures in some areas, could be quantified on non-confocal split-detection AOSLO images. RPE cells were also visible on dark field AOSLO images close to the foveal center. Hypo-reflective gaps of non-waveguiding cones (dark cones) were seen on confocal AOSLO in regions with clinically normal CFP, FIR, FAF and OCT appearance and an intact cone inner segment mosaic in three patients. Conclusion: Dark cones were identified as a possible first sign of retinal disease progression in adult-onset Stargardt disease as these are observed in retinal locations with otherwise normal appearance and outer retinal thickness. This corroborates a previous report where dark cones were proposed as a first sign of progression in childhood-onset Stargardt disease. This also supports the hypothesis that, in Stargardt disease, photoreceptor degeneration occurs before RPE cell death.

Prostanoid signaling in retinal vascular diseases.

The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.

Asymptomatic Ophthalmomyiasis Interna Posterior with Central Pigment Accumulation in the Inner Retina.

PURPOSE: To report a case of ophthalmomyiasis interna posterior which was asymptomatic and had pigment clumps in the inner retina at the macula. METHODS: Single-centre, observational, retrospective case report. RESULTS: A routine refractive error check-up for an asymptomatic 52-year-old Asian Indian woman, who had relied on glasses for 8 years, unfolded a captivating narrative within her retina. This coloured fundus photo unveils mid-peripheral retinal disease with multiple outer retinal atrophic tracts, circumlinear patterns, and intricately intertwined RPE atrophic tracts. These were hyper-autofluorescent on blue autofluorescence. The inferonasal periphery had two-disc diameters of pigmented retinal-choroidal atrophic scar. The macula revealed a collection of black intraretinal pigments in parafoveal areas. The distinct clinical presentation, marked by multiple tracts and unilateral manifestation without disc pallor, hinted at the intriguing possibility of self-resolved "Ophthalmomyiasis interna posterior." CONCLUSION: The course of disease in ophthalmomyiasis interna posterior can be self-limiting and asymptomatic. The presence of inner retinal pigments at foveal and parafoveal areas, possibly due to pigment migration from the peripheral outer retinal tracts, is a rare presentation.

The effect of high-dose erythropoietin perinatally on retinal function in school-aged children born extremely or very preterm.

PURPOSE: To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm. DESIGN: Randomized, double-blind clinical trial follow-up plus cohort study. METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. STUDY POPULATION: extremely or very preterm-born children aged 7-15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period. INCLUSION CRITERIA: participation in an ongoing neuropediatric study (EpoKids), written informed consent (IC). EXCLUSION CRITERIA: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited. INCLUSION CRITERIA: term birth, IC. EXCLUSION CRITERIA: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses. OBSERVATION PROCEDURES: Electroretinography (ERG) was performed with the RETeval device (LKC Technologies, Inc., Gaithersburg MD). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group. MAIN OUTCOME MEASURES: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only). RESULTS: No differences in ERG parameters between EPO (n=52; 104 eyes) and placebo (n=35; 70 eyes) subgroups were observed (all corrected p>0.05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n=52; 104 eyes) subgroup (coefficient/95% confidence interval (CI) = 0.53/0.21 to 0.85 and 0.36/0.13 to 0.60; p = 0.012 and 0.022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% CI = -4.33/-6.88 to -1.78; p = 0.011). Secondary outcomes were comparable across subgroups. CONCLUSIONS: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.

Decrease of alpha crystallin A by miR-325-3p in retinal cells under blue light exposure.

Exposure to blue light can lead to retinal degeneration, causing adverse effects on eye health. Although the loss of retinal cells due to blue light exposure has been observed, the precise molecular mechanisms underlying this process remain poorly understood. In this study, we investigate the role of alpha crystallin A (CRYAA) in neuro-retinal degeneration and their regulation by blue light. We observed significant apoptotic cell death in both the retina of rats and the cultured neuro-retinal cells. The expressions of Cryaa mRNA and protein were significantly down-regulated in the retina exposed to blue light. We identified that miR-325-3p reduces Cryaa mRNA and protein by binding to its 3'-untranslated region (UTR). Up-regulation of miR-325-3p destabilized Cryaa mRNA and suppresses CRYAA, whereas down-regulation of miR-325-3p increased both expressions. Blue light-induced neuro-retinal cell death was alleviated by CRYAA overexpression. These results highlight the critical role of Cryaa mRNA and miR-325-3p molecular axis in blue light-induced retinal degeneration. Consequently, targeting CRYAA and miR-325-3p presents a potential strategy for protecting against blue light-induced retinal degeneration.