Eccentricity Dependency of Retinal Electrophysiological Deficits in People With Episodic Migraine.

Purpose: During the non-attack period, people with migraine may show retinal dysfunction. This study builds on previous work by exploring the possibility of foveal and non-foveal visual field and electroretinographic deficits and determining the overlap in eccentricity of such localized visual deficits in people with migraine. Methods: Visual fields and multifocal electroretinography (mf-ERG) were tested in 27 people with migraine (aged 19-45 years) and 18 non-headache controls (aged 20-46 years). Data were averaged according to 5 concentric rings at < 1.5 degrees (foveal) and 5 degrees, 10 degrees, 15.5 degrees, and 22 degrees eccentricities (non-foveal). Linear mixed effects modelling was used to predict mf-ERG amplitude, mf-ERG peak time, and visual field sensitivity with fixed effects of eye, group, and eccentricity. Results: Foveal mf-ERG responses, and visual field sensitivity across all eccentricities (foveal and non-foveal) were similar between the migraine and control groups (P > 0.05). In contrast, the non-foveal mf-ERG was reduced in amplitude in people with migraine relative to controls (P < 0.001), and this group difference depended on eccentricity (P < 0.001) - most prominently, in the parafoveal region (ring 2, P = 0.001). Conclusions: Retinal electrophysiological deficits were observed in people with migraine in the parafoveal region (between 1.5 degrees and 5 degrees eccentricity), without corresponding visual field deficits. This suggests a spatially localized area of retinal neuronal dysfunction in people with migraine that is insufficient to manifest as a visual field sensitivity loss using standard perimetric methods. Our study highlights the added confound of migraine when conducting standard clinical retinal electrophysiological tests for conditions such as glaucoma, particularly non-foveally.

THE PROGNOSTIC SIGNIFICANCE OF ACUTE HENLE FIBER LAYER HYPERREFLECTIVITY IN PLACOID DISEASES.

PURPOSE: To investigate the pathophysiology and prognostic significance of acute Henle fiber layer (HFL) hyperreflectivity in placoid diseases by examining its relationship with impaired choroidal flow and persistent photoreceptor disruption. METHODS: Retrospective-prospective observational study on patients with placoid diseases. Indocyanine green angiography and optical coherence tomography were performed during the acute phase and follow-up. Impaired choroidal flow, HFL hyperreflectivity, and persistent ellipsoid zone disruption, their colocalization index, and their associations with initial and final visual acuity were explored. RESULTS: Sixteen eyes from eight patients (mean age, 25.3 ± 6.44 years) were included (median follow-up, 13.5 months). Quantitative analysis revealed significant correlations between areas of impaired choroidal flow, HFL hyperreflectivity, and persistent ellipsoid zone disruption (correlation coefficients of 0.69, 0.63, and 0.46, respectively). Impaired choroidal flow area exceeded HFL hyperreflectivity (P = 0.002) and ellipsoid zone disruption (P = 0.003). A noteworthy 94% nonrandom overlap between HFL hyperreflectivity and ellipsoid zone disruption was observed. Worse initial visual acuity correlated with foveal involvement (P = 0.0002), thicker choroid (P = 0.001), larger impaired choroidal flow areas (P = 0.02), and thinner outer retina post lesion inactivation (P = 0.04). CONCLUSION: Henle fiber layer hyperreflectivity predicted photoreceptor recovery potential in placoid diseases. If HFL hyperreflectivity corresponds to acute HFL damage, it may suggest more severe involvement of the entire photoreceptor length.

Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

Effects of Acute High-Altitude Exposure on Morphology and Function of Retinal Ganglion Cell in Mice.

Purpose: High altitude retinopathy (HAR) is a retinal functional disorder caused by inadequate adaptation after exposure to high altitude. However, the cellular and molecular mechanisms underlying retinal dysfunction remain elusive. Retinal ganglion cell (RGC) injury is the most important pathological basis for most retinal and optic nerve diseases. Studies focusing on RGC injury after high-altitude exposure (HAE) are scanty. Therefore, the present study sought to explore both functional and morphological alterations of RGCs after HAE. Methods: A mouse model of acute hypobaric hypoxia was established by mimicking the conditions of a high altitude of 5000 m. After HAE for 2, 4, 6, 10, 24, and 72 hours, the functional and morphological alterations of RGCs were assessed using retinal hematoxylin and eosin (H&E) sections, retinal whole mounts, transmission electron microscopy (TEM), and the photopic negative response (PhNR) of the electroretinogram. Results: Compared with the control group, the thickness of the ganglion cell layer and retinal nerve fiber layer increased significantly, RGC loss remained significant, and the amplitudes of a-wave, b-wave, and PhNR were significantly reduced after HAE. In addition, RGCs and their axons exhibited an abnormal ultrastructure after HAE, including nuclear membrane abnormalities, uneven distribution of chromatin in the nucleus, decreased cytoplasmic electron density, widening and vacuolization of the gap between axons, loosening and disorder of myelin sheath structure, widening of the gap between myelin sheath and axon membrane, decreased axoplasmic density, unclear microtubule and nerve fiber structure, and abnormal mitochondrial structure (mostly swollen, with widened membrane gaps and reduced cristae and vacuolization). Conclusions: The study findings confirm that the morphology and function of RGCs are damaged after HAE. These findings lay the foundation for further study of the specific molecular mechanisms of HAR and promote the effective prevention.

Evidence for the Hepato-Retinal Axis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Liver health has been reported to be associated with retinal pathology in various ways. These include deposition of retino-toxins, neovascular drive, and disruption of the blood-retina barrier. Extrahepatic synthesis of implicated molecules and hemodynamic changes in liver dysfunction are also considered. The objective was to review the current evidence for and against a hepato-retinal axis that may guide further areas of preclinical and clinical investigation. METHODS: This was a systematic review. PubMed and Cochrane were queried for English language studies examining the connection between hepatic dysfunction and retinal pathology. RESULTS: Fourteen studies were included and examined out of 604 candidate publications. The studies selected include preclinical studies as well as clinical case series and studies. CONCLUSIONS: Several liver pathologies may be linked to retinal pathology as mediated by hepatically synthesized molecules. The hepato-retinal axis may be present and further, targeted studies of the axis are warranted. [Ophthalmic Surg Lasers Imaging Retina 2024;55:587-596.].

Performance of Extended Depth of Focus Intraocular Lens in Eyes with Preexisting Retinal Disease.

INTRODUCTION: Extended depth of focus (EDOF) intraocular lens (IOL) offers improved near and intermediate vision, aiming to reduce spectacle dependence in cataract patients. This research aimed to evaluate the performance of EDOF IOL in patients with retinal pathologies following cataract surgery. METHODS: The medical charts of thirty-three eyes with retinal pathologies and 100 healthy eyes that underwent cataract extraction with implantation of an EDOF IOL and had at least 3 weeks of postoperative follow-up were retrospectively included. Patients' overall satisfaction, spectacle dependence, visual perception, and side effects were evaluated with a self-reported questionnaire. RESULTS: Mean uncorrected visual acuities (LogMAR) were significantly better in the healthy eyes compared with the eyes with retinal pathologies: 0.05 and 0.10, p = 0.011 (distance), 0.06 and 0.16, p = 0.001 (intermediate), and 0.20 and 0.28, p = 0.026 (near), respectively. No or rare use of spectacles for any distance was reported by 71% and 38% of patients, respectively (p = 0.004). Haloes/glare were reported by 17% and 23%, respectively (p = 0.556); only in 7% and 4% it was clinically disturbing (p > 0.999). The same IOL would be chosen again in 77% and 73% of patients, respectively, (p = 0.550). CONCLUSION: Patients with retinal pathologies who were implanted with an EDOF IOL demonstrated excellent distant uncorrected visual results with reasonable intermediate and near uncorrected visual results alongside high satisfaction; however, results were inferior to those of the control healthy eyes.

Pre-processing visual scenes for retinal prosthesis systems: A comprehensive review.

BACKGROUND: Retinal prostheses offer hope for individuals with degenerative retinal diseases by stimulating the remaining retinal cells to partially restore their vision. This review delves into the current advancements in retinal prosthesis technology, with a special emphasis on the pivotal role that image processing and machine learning techniques play in this evolution. METHODS: We provide a comprehensive analysis of the existing implantable devices and optogenetic strategies, delineating their advantages, limitations, and challenges in addressing complex visual tasks. The review extends to various image processing algorithms and deep learning architectures that have been implemented to enhance the functionality of retinal prosthetic devices. We also illustrate the testing results by demonstrating the clinical trials or using Simulated Prosthetic Vision (SPV) through phosphene simulations, which is a critical aspect of simulating visual perception for retinal prosthesis users. RESULTS: Our review highlights the significant progress in retinal prosthesis technology, particularly its capacity to augment visual perception among the visually impaired. It discusses the integration between image processing and deep learning, illustrating their impact on individual interactions and navigations within the environment through applying clinical trials and also illustrating the limitations of some techniques to be used with current devices, as some approaches only use simulation even on sighted-normal individuals or rely on qualitative analysis, where some consider realistic perception models and others do not. CONCLUSION: This interdisciplinary field holds promise for the future of retinal prostheses, with the potential to significantly enhance the quality of life for individuals with retinal prostheses. Future research directions should pivot towards optimizing phosphene simulations for SPV approaches, considering the distorted and confusing nature of phosphene perception, thereby enriching the visual perception provided by these prosthetic devices. This endeavor will not only improve navigational independence but also facilitate a more immersive interaction with the environment.

DISCREPANCY BETWEEN FUNDUS AUTOFLUORESCENCE ABNORMALITY AND VISUAL FIELD LOSS IN BIETTI CRYSTALLINE DYSTROPHY.

PURPOSE: The aim of this study was to explore the potential benefits of retinal pigment epithelium replacement therapy in patients with Bietti crystalline dystrophy (BCD) by assessing the disease pathology with the distinctive relationship between fundus autofluorescence (FAF) abnormality and visual field defect. METHODS: Sixteen eyes from 16 patients with BCD and 16 eyes from 16 patients with RHO-associated retinitis pigmentosa were included. Fundus autofluorescence, optical coherence tomography, and Goldmann perimetry results were retrospectively reviewed and assessed using image analyses. RESULTS: In patients with BCD, the FAF abnormality area was not correlated with the overall visual field defect area and median overall visual field defect area (57.5%) was smaller than FAF abnormality area (98.5%). By contrast, the ellipsoid zone width was significantly correlated with the central visual field area (r = 0.806, P < 0.001). In patients with RHO-associated retinitis pigmentosa, the FAF abnormality area and ellipsoid zone width were significantly correlated with the overall visual field defect area (r = 0.833, P < 0.001) and central visual field area (r = 0.887, P < 0.001), respectively. CONCLUSION: The FAF abnormality shown in patients with BCD involves retinal pigment epithelium degeneration without complete loss of photoreceptors or visual function. These results suggest that patients with BCD are good candidates for retinal pigment epithelium replacement therapy for preservation of residual visual function.

The Complement System as a Therapeutic Target in Retinal Disease.

The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is imperative for ensuring the integrity and homeostasis of the retina. While this system is critical for proper host defense and retinal integrity, it has also been found that dysregulation of this system may lead to certain retinal pathologies, including geographic atrophy and diabetic retinopathy. Targeting components of the complement system for retinal diseases has been an area of interest, and in vivo, ex vivo, and clinical trials have been conducted in this area. Following clinical trials, medications targeting the complement system for retinal disease have also become available. In this manuscript, we discuss the pathophysiology of complement dysfunction in the retina and specific pathologies. We then describe the results of cellular, animal, and clinical studies targeting the complement system for retinal diseases. We then provide an overview of complement inhibitors that have been approved by the Food and Drug Administration (FDA) for geographic atrophy. The complement system in retinal diseases continues to serve as an emerging therapeutic target, and further research in this field will provide additional insights into the mechanisms and considerations for treatment of retinal pathologies.

The association of microvascular disease and endothelial dysfunction with vertebral trabecular bone mineral density : The MESA study.

Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. PURPOSE: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. METHODS: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. RESULTS: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. CONCLUSION: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures.

Vitamin A deficiency retinopathy in the setting of celiac disease and liver fibrosis.

PURPOSE: Vitamin A is a lipid-soluble compound that is critical in maintaining phototransduction. Ocular manifestations of hypovitaminosis A may present with anterior segment signs of xeropthalmia, with advanced cases also causing classic retinal and electrophysiologic changes of vitamin A deficiency retinopathy. We present a case of vitamin A deficiency retinopathy, with corresponding retinal imaging and electrophysiology, in an adult patient with celiac disease and liver fibrosis. METHODS: A single case report was conducted in Toronto, Canada. RESULTS: A 77-year-old male with known celiac disease and liver fibrosis presented progressively worsening vision noticed primarily when driving. Vision was 20/50 OD and 20/200 OS. Bitot spots were noted on anterior segment examination. Fundus photography demonstrated bilateral peripheral macular hypopigmentation and far-peripheral granular retinal hypopigmentation with focal yellow dots and hyper-pigmented deposits. Optical coherence tomography (OCT) imaging demonstrated indistinct outer retinal banding with mild outer nuclear layer thinning, focal hyper-reflective deposits, and a thin choroid bilaterally. Full-field electroretinography (ERG) testing demonstrated reduced rod-isolated and combined rod-cone response amplitudes, and multifocal ERG testing demonstrated blunted individual responses throughout the field. The patient was treated with pulse vitamin A therapy. After 6 months of therapy, ERG responses were back within reference range, and the outer retinal changes reversed; visual acuity improved to 20/30 OD and 20/40 OS. CONCLUSION: This case represents the classic findings of vitamin A deficiency retinopathy on fundus examination and electrophysiologic testing secondary to gastrointestinal pathology. Prompt treatment of high dose vitamin A supplementation led to improvement of full-field and multifocal ERG results, as well as reconstitution of outer retinal architecture.

RDH5 and RLBP1-Associated Inherited Retinal Diseases: Refining the Spectrum of Stationary and Progressive Phenotypes.

PURPOSE: To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations. DESIGN: Retrospective single-center cohort study. METHODS: Twenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing. RESULTS: The median (interquartile ranges) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy (MA) was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm3 (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm3/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference between the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of MA. CONCLUSIONS: Progressive MA in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with MA. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.

Electrodiagnostic tests of the visual pathway and applications in neuro-ophthalmology.

This article describes the main visual electrodiagnostic tests relevant to neuro-ophthalmology practice, including the visual evoked potential (VEP), and the full-field, pattern and multifocal electroretinograms (ffERG; PERG; mfERG). The principles of electrophysiological interpretation are illustrated with reference to acquired and inherited optic neuropathies, and retinal disorders that may masquerade as optic neuropathy, including ffERG and PERG findings in cone and macular dystrophies, paraneoplastic and vascular retinopathies. Complementary VEP and PERG recordings are illustrated in demyelinating, ischaemic, nutritional (B12), and toxic (mercury, cobalt, and ethambutol-related) optic neuropathies and inherited disorders affecting mitochondrial function such as Leber hereditary optic neuropathy and dominant optic atrophy. The value of comprehensive electrophysiological phenotyping in syndromic diseases is highlighted in cases of SSBP1-related disease and ROSAH (Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and Headache). The review highlights the value of different electrophysiological techniques, for the purposes of differential diagnosis and objective functional phenotyping.

[Cell loss in retinal ischemia is associated with increased necroptosis]. / Zellverlust bei retinaler Ischämie ist assoziiert mit vermehrter Nekroptose.

BACKGROUND: Retinal ischemia plays a central pathophysiological role in numerous eye diseases, such as glaucoma. In addition to apoptosis, autophagy, necroptosis and ferroptosis are among the cell death mechanisms of ischemia; however, their role is not clearly understood and controversially discussed. OBJECTIVE: The aim of this study is to gain an improved understanding of the role of alternative cell death mechanisms such as autophagy and necroptosis after retinal ischemia. Based on this, future autophagy-based or necroptosis-based therapeutic approaches could be developed. MATERIAL AND METHODS: Retinal ischemia reperfusion was induced in one eye of 6 to 8­week-old rats by temporarily increasing the intraocular pressure to 140 mm Hg (60 min), followed by reperfusion. The untreated contralateral eye served as a control. Retinas after ischemia and control retinas were examined 7 days after ischemia immunohistochemically with markers for retinal ganglion cells (RGC), astrocytes (GFAP) as well as an autophagy (LAMP1) and a necroptosis marker (RIPK3) (n = 6/group). RESULTS: Ischemia reperfusion resulted in both significant RGC loss (p ≤ 0.001) and a significant increase of astrocyte area (p = 0.026) after 7 days. Interestingly, the number of autophagic LAMP1 positive cells was unchanged 7 days after ischemia (p = 0.272), whereas the number of necroptotic RIPK3 positive cells was significantly increased (p ≤ 0.001). CONCLUSION: Necroptotic processes appear to be activated 7 days after ischemia reperfusion, contributing to retinal cell death and activation of astrocytes. Late autophagic processes are not activated 7 days after ischemia. Necroptosis-associated parameters could therefore be targeted as an early therapeutic approach after ischemia in the future.

The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients.

Purpose: Recent studies have shown that the retinal pigment epithelium (RPE) relies on fatty acid oxidation (FAO) for energy, however, its role in overall retinal health is unknown. The only FAO disorder that presents with chorioretinopathy is long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Studying the molecular mechanisms can lead to new treatments for patients and elucidate the role of FAO in the RPE. This paper characterizes the chorioretinopathy progression in a recently reported LCHADD mouse model. Methods: Visual assessments, such as optokinetic tracking and fundus imaging, were performed in wildtype (WT) and LCHADD mice at 3, 6, 10, and 12 months of age. Retinal morphology was analyzed in 12-month retinal cross-sections using hematoxylin and eosin (H&E), RPE65, CD68, and TUNEL staining, whereas RPE structure was assessed using transmission electron microscopy (TEM). Acylcarnitine profiles were measured in isolated RPE/sclera samples to determine if FAO was blocked. Bulk RNA-sequencing of 12 month old male WT mice and LCHADD RPE/sclera samples assessed gene expression changes. Results: LCHADD RPE/sclera samples had a 5- to 7-fold increase in long-chain hydroxyacylcarnitines compared to WT, suggesting an impaired LCHAD step in long-chain FAO. LCHADD mice have progressively decreased visual performance and increased RPE degeneration starting at 6 months. LCHADD RPE have an altered structure and a two-fold increase in macrophages in the subretinal space. Finally, LCHADD RPE/sclera have differentially expressed genes compared to WT, including downregulation of genes important for RPE function and angiogenesis. Conclusions: Overall, this LCHADD mouse model recapitulates early-stage chorioretinopathy seen in patients with LCHADD and is a useful model for studying LCHADD chorioretinopathy.

Alzheimer's disease pathophysiology in the Retina.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid ß-protein (Aß) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aß deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Spontaneous Resolution of a Combined Hamartoma in a One-Year-Old Child.

The combined hamartoma of the retina and the retinal pigment epithelium (CHR-RPE) is a rare but histologically benign tumor of which no clear consensus exists regarding its appropriate management. Most commonly CHR-RPE presents unilaterally in children as an elevated, pigmented lesion associated with vascular tortuosity and an epiretinal membrane (ERM). Patients may have decreased visual acuity (VA) in the affected eye, notably if the overlying ERM extends into the macula. For this reason, surgical intervention in the form of ERM removal has been pursued with notable success. Still, those who pursue observation cite the interwoven nature of the overlying glial membrane within the dysplastic retina, complicating surgery and accounting for variability in post-operative VA success. Given the rarity of the tumor coupled with the scarcity of data on its natural evolution, clinicians who pursue observation cannot know for sure whether withholding surgical management is predisposing their patients to worse visual outcomes as compared to those patients who undergo ERM peel as first-line therapy. This case report will discuss an infant with clinically diagnosed CHR-RPE whose lesion showed significant regression after 6 months of observation. This success story should cause ophthalmologists to reconsider the management options at their disposal when faced with a case of CHR-RPE, and to call for further research to better define the risks of observation over surgical intervention. [Ophthalmic Surg Lasers Imaging Retina 2024;55:471-473.].

Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction.

Retinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.