Choroidal Neovascularization Research Articles

Comparative study between swept-source and spectral-domain OCTA for imaging of choroidal neovascularization in age-related macular degeneration

AIM: To compare the differences of choroidal neovascularization (CNV) measurements between swept-source and spectral-domain optical coherence tomography angiography (SS-OCTA and SD-OCTA) in neovascular age-related macular degeneration (nAMD) and the imaging reliability of the two devices. METHODS: Prospective comparative study. SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3×3 and 6×6 mm2 centered on the neovascularization. Only qualified images were chosen and the border of CNV was manually delineated by two graders independently. The area of CNV (ACNV), vascular perfusion density (PD), and vessel length density (VLD) within the delineation were calculated using Image J. The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis. The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient (ICC). RESULTS: A total of 18 patients (22 eyes) with nAMD were included. The measurements of ACNV, PD, and VLD were 7.247±4.586 and 4.901±3.741 mm2, 43.202±9.636 and 34.904±10.489, 6.339±1.228 and 5.908±1.741 mm-1 for SS-OCTA and SD-OCTA, respectively. The differences between the two devices were 2.346±3.030 mm2 (Z= -3.782, P<0.0001), 8.298±14.160 (Z=-2.419, P=0.016), and 0.431±2.114 mm-1 (Z=-0.828, P=0.408) for ACNV, PD and VLD, respectively. The ICC between two graders were 0.893 (P<0.001), 0.902 (P<0.001), 0.885 (P<0.001) for ACNV, PD, VLD in SS-OCTA, and 0.971 (P<0.001), 0.976 (P<0.001), 0.973 (P<0.001) in SD-OCTA, respectively. CONCLUSION: Both OCTA devices have high imaging reliability. Compared with SD-OCTA, SS-OCTA has a larger ACNV measurements, but doesn't show better resolution of internal vessels of CNV and well signal strength.

Short-term fluctuation of intraocular pressure and influencing factors following intravitreal injection in patients with retinal vascular diseases

AIM: To investigate the patterns of short-term intraocular pressure (IOP) fluctuations and identify the contributing factors following intravitreal injection in patients with retinal vascular diseases. METHODS: Totally 81 patients were enrolled in this case control study. Eyes were categorized into 7 groups, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), idiopathic choroidal neovascularization (CNV), proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), macular edema secondary to branch (BVOME) and central (CVOME) retinal vein occlusion. IOP was measured in all patients using rebound tonometer at 7 preset time points perioperatively. Additionally, based on the administered medication, the eyes were classified into three treatment groups, including dexamethasone intravitreal implant (IVO), intravitreal conbercept (IVC), and intravitreal ranibizumab (IVR). To compare IOP values at various time points across groups, we employed one-way ANOVA, independent sample t-test or χ2 test and multivariate logistic regression analysis. RESULTS: Peak IOP values across all groups were observed at 40s, and 5min after intravitreal injection. Statistical differences in IOP were detected at the 5min among the 7 indication groups (F=2.50, P=0.029). When examing the impact of medications, the IVO group exhibited lower average IOP values at both 40s and 5min compared to the IVC and IVR groups (P<0.001; P=0.007). The IOP values at 40s and 5min were significantly higher in BVOME and CVOME group compared to non-retinal vein occlusion-secondary macular edema (RVOME) group (P<0.001). Multivariate logistic regression analysis further confirmed that IOP measurement at 40s was significantly higher in CVOME group than in non-RVOME group (OR=1.64, 95%CI: 1.09-2.47; P=0.018). CONCLUSION: Needle size plays a crucial role in the transient changes of IOP following intravitreal injection. Before administering intravitreal injection to patients with central retinal vein occlusion, it is essential to exclude any underlysing causes of increased IOP.

Outlier ophthalmologists in the treatment of neovascular age-related macular degeneration with intravitreal therapy

BackgroundTo compare individual ophthalmologists grouped as outliers or non-outliers based on the mean 12-month visual acuity (VA) outcomes for their patients with neovascular age-related macular degeneration (nAMD).MethodsThis prospectively designed database...

Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization.

Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating various neovascularization-related diseases. In this study, we devised a CRISPR/Cas9 delivery system employing the nucleic acid aptamer AS1411 as a targeting moiety and exosome-liposome hybrid nanoparticles as carriers (CAELN). Exploiting the binding affinity between AS1411 and nucleolin on endothelial cell surfaces, the delivery system was engineered to specifically target the glutamine synthetase gene (GLUL), thereby attenuating GS levels and continuously suppressing CNV. CAELN exhibited spherical and uniform dispersion. In vitro cellular investigations demonstrated gene editing efficiencies of CAELN ranging from 42.05 to 55.02% and its capacity to inhibit neovascularization in HUVEC cells. Moreover, in vivo pharmacodynamic studies conducted in CNV rabbits revealed efficacy of CAELN in restoring the thickness of intra- and extranuclear tissues. The findings suggest that GS is a novel target for the inhibition of pathological CNV, while the development of AS1411-modified exosome-liposome hybrid nanoparticles represents a novel delivery method for the treatment of neovascular-related diseases.

The perspective of ceRNA regulation of circadian rhythm on choroidal neovascularization

Abnormal growth of blood vessels (choroidal neovascularization) can lead to age-related macular degeneration (AMD) and eventually cause vision loss due to detachment of the retinal pigmented epithelium. This indicates that choroidal neovascularization is important for the treatment of AMD. The circadian clock in the mammalian retina is responsible for controlling various functions of the retina, enabling it to adjust to changes in light and darkness. Recent studies have revealed a potential connection between the circadian clock and eye diseases, although a cause-and-effect relationship has not been definitively established. C57BL/6J male mice (aged 6 weeks) were randomly divided into two groups (Control group: 9:00–21:00 light period (300 lx); Jet lag group: 8-hour phase advance once every 4 days). A laser-induced CNV model was created after 2 weeks of feeding in a controlled or jet-lagged environment. Then, full transcriptome sequencing was performed. The pathways regulated by differentially expressed mRNAs were identified by GO analysis and GSEA. Further protein networks were constructed with the STRING database and Cytoscape software. WGCNA was used to further explore the co-expression modules of these differential genes and the correlation between these differential genes and phenotypes. ceRNA networks were constructed with miRanda and TargetScan. The pathways associated with the overlapping differentially expressed mRNAs in the ceRNA network were identified, and the hub genes were validated by qPCR. A total of 661 important DEGs, 31 differentially expressed miRNAs, 106 differentially expressed lncRNAs and 87 differentially expressed circRNAs were identified. GO and GSEA showed that the upregulated DEGs were mainly involved in reproductive structure development and reproductive system development. The STRING database and Cytoscape were used to determine the protein interaction relationships of these DEGs. WGCNA divided the expression of these genes into several modules and screened the hub genes of each module separately. Furthermore, a ceRNA network was constructed. GO analysis and GSEA showed that these target DEmRNAs mainly function in wound healing, cell spreading, epiboly involved in wound healing, epiboly, and morphogenesis of an epithelial sheet. Finally, ten key genes were identified, and their expression patterns were confirmed by real-time qPCR. In this study, we investigated the regulatory mechanism of ceRNAs in choroidal neovascularization according to different light-dark cycles in the eyeball.

VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept

Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD. Here, we report that expression of ANGPTL4 in patients with nvAMD increases following treatment with anti-VEGF therapy and that this increase is dependent on accumulation of hypoxia-inducible factor (HIF)-1α in response to inhibition of VEGF/KDR signaling in the retinal pigment epithelium (RPE). We therefore explored HIF-1 inhibition with 32-134D, a recently developed pharmacologic HIF-inhibitor, for the treatment of nvAMD. 32-134D prevented the expression of both VEGF and ANGPTL4 and was at least as effective as aflibercept in treating CNV in mice. Moreover, by preventing the increase in HIF-1α accumulation in the RPE in response to anti-VEGF therapy, combining 32-134D with aflibercept was more effective than either drug alone for the treatment of CNV. Collectively, these results help explain why many patients with nvAMD respond inadequately to anti-VEGF therapy and suggest that the HIF inhibitor 32-134D will be an effective drug-alone or in combination with current anti-VEGF therapies-for the treatment of patients with this blinding disease.

Two macular holes due to choroidal neovascularization after pars plana vitrectomy with internal limiting membrane peeling

Introduction: To present a case of two macular holes (MHs) with myopic choroidal neovascularization (CNV) lesion. Case Presentation: A single case was evaluated. A 72-year-old woman presented with two small MHs in her left eye. One year ago, she had undergone vitrectomy for myopic foveal schisis, and a significant reduction of the schisis and a CNV lesion was observed after surgery. On examination, OCT (optical coherence tomography) showed the atrophic CNV and two MHs were located upper and lower close to the edge of the CNV. A PPV (pars plana vitrectomy) with two free ILM (internal limiting membrane) flaps implant was performed in her left eye. At 3 months after surgery, the two macular holes were both closed and the BCVA (best corrected visual acuity) was improved. Conclusions: Two MHs secondary to the regression of CNV after primary PPV combined with complete ILM peeling in eyes with macular schisis.

ONS-5010 (bevacizumab-vikg) Safety and Efficacy in Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration.

This was a prospective multicenter, randomized, double-masked, active-controlled study, the aim of which was to demonstrate the efficacy and safety of intravitreal ONS-5010 (bevacizumab-vikg) in eyes with neovascular age-related macular degeneration (nAMD). This was a phase III trial on ONS-5010 (NORSE TWO). Treatment-naïve nAMD patients aged 50 years and older with a best-corrected distance visual acuity (BCVA) of 25 to 67 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and evidence of disease activity were included. Subjects randomized to ONS-5010 received monthly intravitreal doses of 1.25 mg of ONS-5010, bevacizumab-vikg (Outlook Therapeutics) for 12 months. Subjects randomized to ranibizumab received 0.50 mg of ranibizumab on days 0, 30, 60, 150, and 240 based on the PIER study dosing regimen. The primary end point was the proportion of subjects who gained ≥ 15 letters from baseline in BCVA at 11 months, and evaluating the safety and tolerability of intravitreal injections of ONS-5010 administered monthly from baseline to 12 months. One hundred thirteen subjects were included in the ONS-5010 group and 115 subjects were included in the ranibizumab group. Respectively, 41.7% and 23.1% of patients gained ≥ 15 letters (3 lines) of visual acuity, with a risk difference of 0.1859 [95% CI = 0.0442, 0.3086]; P = 0.0052. The change in BCVA from baseline to 11 months was found to be 11.2 ± 12.19 and 5.8 ± 14.80 ETDRS letters, respectively. The number of subjects gaining ≥ 5 and ≥ 10 letters and subjects losing < 15 letters was significantly higher in the ONS-5010 group. Similarly, subjects with a Snellen visual acuity equivalent of 20/200 (35 ETDRS letters) or worse at 11 months were significantly fewer in the ONS-5010 group. Only one subject in the ONS-5010 group had a study-related serious ocular adverse event (SAE), namely, elevated intraocular pressure. The most common adverse event in the ONS-5010 group was conjunctival hemorrhage (8.8%), and reduced visual acuity in the ranibizumab group (12.2%). In the prescribed treatment plan, ONS-5010 exhibited strong effectiveness in improving or stabilizing visual acuity and was also well tolerated. Bevacizumab and ranibizumab displayed a comparable safety profile. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Automatic Method of Macular Diseases Detection Using Deep CNN-GRU Network in OCT Images

Abstract The increasing development of Deep Learning mechanism allowed ones to create semi-fully or fully automated diagnosis software solutions for medical imaging diagnosis. The convolutional neural networks are widely applied for central retinal diseases classification based on OCT images. The main aim of this study is to propose a new network, Deep CNN-GRU for classification of early-stage and end-stages macular diseases as age-related macular degeneration and diabetic macular edema (DME). Three types of disorders have been taken into consideration: drusen, choroidal neovascularization (CNV), DME, alongside with normal cases. The created automatic tool was verified on the well-known Labelled Optical Coherence Tomography (OCT) dataset. For the classifier evaluation the following measures were calculated: accuracy, precision, recall, and F1 score. Based on these values, it can be stated that the use of a GRU layer directly connected to a convolutional network plays a pivotal role in improving previously achieved results. Additionally, the proposed tool was compared with the state-of-the-art of deep learning studies performed on the Labelled OCT dataset. The Deep CNN-GRU network achieved high performance, reaching up to 98.90% accuracy. The obtained results of classification performance place the tool as one of the top solutions for diagnosing retinal diseases, both early and late stage.

Reactive Oxygen Species Responsive Supramolecular Prodrug Eyedrops for the Treatment of Choroidal Neovascularization.

Choroidal neovascularization (CNV) represents a hallmark of neovascular fundus diseases, including age-related macular degeneration and diabetic retinopathy. Traditional eyedrops have encountered formidable challenges in treating CNV, primarily due to their extremely poor intraocular bioavailability and potential adverse off-target effects. Herein, an ocular-permeable supramolecular prodrug eyedrop (Di-DAS/P-PCD) has been developed for the on-demand delivery of antiangiogenic agents in the oxidative microenvironment of CNV. The eyedrop nanoformulation is composed of cell-penetrating peptide-modified PEGylated cyclodextrin (P-PCD) and reactive oxygen species (ROS)-sensitive antiangiogenic dasatinib prodrug Di-DAS. In a laser-induced CNV mouse model, daily instillation of Di-DAS/P-PCD has achieved remarkable penetration into the choroid and significantly suppressed CNV growth while exhibiting a good biocompatibility profile. Our results highlight the potential of the supramolecular prodrug eyedrops as a versatile approach for the targeted treatment of CNV and other neovascular eye disorders.

Self-supervised based clustering for retinal optical coherence tomography images.

In response to the inadequacy of manual analysis in meeting the rising demand for retinal optical coherence tomography (OCT) images, a self-supervised learning-based clustering model was implemented. A public dataset was utilized, with 83,484 OCT images with categories of choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal fundus. This study employed the Semantic Pseudo Labeling for Image Clustering (SPICE) framework, a self-supervised learning-based method, to cluster unlabeled OCT images into binary and four categories, and the performances were compared with baseline models. We also analysed feature distribution using t-SNE, and explored the cluster centers, attention maps, and misclassified images. In addition, DME and CNV subsets were clustered binarily, and the results were interpreted by two retinal specialists. SPICE demonstrated superior performance in binary and four categories classification tasks, achieving the accuracy of 0.886 and 0.846, respectively. In t-SNE analysis, the four types exhibited significant clustering into distinct groups. The cluster centers corresponded to the human labels, and the heat map revealed that the model focused on important biomarkers. The misclassified images exposed similar features to the inaccurate classes. The model also grouped DME and CNV into two distinct categories respectively. Self-supervised clustering effectively distinguished disease variances and revealed common features, with a notable capability to detect disease heterogeneity through biomarkers.

Targeting the VEGFR2 signaling pathway for angiogenesis and fibrosis regulation in neovascular age-related macular degeneration

Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis.

Successful Aflibercept Treatment for Choroidal Neovascularization in a Rare Case of Optic Disc Melanocytoma

Successful Aflibercept Treatment for Choroidal Neovascularization in a Rare Case of Optic Disc Melanocytoma

Turn-Adopting Peptidomimetic as a Formyl Peptide Receptor-1 Antagonist.

The design, synthesis, and characterization of a new peptidomimetic acting as a formyl peptide receptor (FPR1) antagonist (N-19004) are herein reported. The molecule has been identified with docking studies of the highly potent FPR1 antagonist UPARANT on human receptor. N-19004 recapitulates all pharmacophoric groups necessary for recognition into a minimal structure, with a crucial role of the 2,6-diamino-thiophenyl scaffold mimicking the positions of Cα atoms of Arg residues in the turned Arg-Aib-Arg segment of UPARANT. N-19004 demonstrated to interfere with the biological properties of FPR1 both in vitro and in vivo. In a mouse model of choroidal neovascularization, N-19004 markedly reduced the size of laser-induced choroidal lesions, with reabsorption of the edema regions by a systemic administration route.

Microsecond Pulsing Laser for Choroidal Neovascularization Associated with Central Serous Chorioretinopathy

Purpose To analyze the efficacy and safety of microsecond pulsing laser therapy (MLT) in the management of central serous chorioretinopathy (CSCR) complicated by choroidal neovascularization (CNV). Methods Patients with CSCR complicated by CNV defined as the presence of characteristic OCT angiography features were randomly assigned to either study or control group. All patients of the study group underwent MLT targeting CNV area using navigated laser system followed by at least 6-month follow-up. Sham treatment was performed in the control group. No other treatment or anti-VEGF therapy was used during the follow-up. Main outcome measure was complete resolution of subretinal fluid at the end of follow-up. Results Twenty-three eyes (13 males and 10 females, mean age 58.2 ± 8.0 years) with a mean CNV area 0.62 ± 0.77 mm2 were included in the study group. Fourteen (60.9%) patients achieved complete resolution of SRF, five (21.7%) patients demonstrated some reduction of SRF, and four (17.4%) patients demonstrated no improvement after MLT in the study group. Twelve eyes (8 males and 4 females, mean age 59.8 ± 4.6 years) were included in the control group where none of them demonstrated resolution of SRF at the end of the follow-up (p = 0.0018 compared to the study group). No adverse effects, such as changes of CNV size, deterioration of exudation, or decline in visual acuity were observed in the study group. Conclusion Microsecond pulsing laser is an effective and safe option for the treatment of CSCR complicated by relatively small CNV and achieves complete resolution of SRF in 61% of cases.

Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration.

Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents a challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds of developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, and inflammation across multiple diseases. This preclinical study assessed metformin's impact on vessel growth using choroidal explants before exploring IVT metformin's effects on laser-induced CNV and light-induced retinal degeneration in C57BL/6J and BALB/cJ mice, respectively. Metformin reduced new vessel growth in choroidal explants in a dose-dependent relationship. Following laser induction, IVT metformin suppressed CNV and decreased peripheral infiltration of IBA1+ macrophages/microglia. Furthermore, IVT metformin protected against retinal thinning in response to light-induced degeneration. IVT metformin downregulated genes in the choroid and retinal pigment epithelium which are associated with angiogenesis and inflammation, two key processes that drive nAMD progression. These findings underscore metformin's capacity as an anti-angiogenic and neuroprotective agent, demonstrating this drug's potential as an accessible option to help manage nAMD.

Choroidal Infiltration in Erdheim-Chester Disease: A Case Series

Purpose: We describe two cases of choroidal involvement in patients with Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis. Methods: Short case series. Results: The first patient was a 25-year-old man with asymptomatic ECD at the level of bones, lung, and central nervous system. Fundus examination revealed bilateral yellowish choroidal infiltration in the superior macula and nasal mid-periphery. After initial mild enlargement of the choroidal lesions, treatment with weekly subcutaneous pegylated interferon α2a (PEG-IFN) was started inducing partial regression of the lesions. The second patient was a 45-year-old man with ECD involving the left orbit, maxillary sinus, heart, blood vessels, kidney, retroperitoneum, bones and testes. Fundus examination of the left eye showed choroidal folds. Macular spectral-domain optical coherence tomography confirmed the folds and revealed underlying choroidal infiltration. Final ocular diagnosis was left choroidal, scleral, and orbital involvement. The patient was initially treated with PEG-IFN, and later with cobimetinib, a MEK inhibitor, with favorable results. Neither patient developed choroidal neovascularization (CNV) during the follow-up. Conclusions: ECD is a rare multisystem disorder that can present with ocular involvement, including orbital masses, xanthelasma-like lesions, and occasionally, choroidal infiltrates. Early recognition and prompt treatment can lead to improvement of ophthalmic and systemic symptoms and prevent further complications. We recommend treating patients with choroidal ECD, regardless of the presence of symptoms, considering these patients are at increased risk of developing CNV.

NR2E3-Associated Retinopathy Presenting with Bilateral Choroidal Neovascularization

Purpose: We describe an atypical presentation of an 11-year-old female with enhanced S-cone syndrome (ESCS). Methods: Case report. The patient underwent a thorough ophthalmic examination and investigations such as colour fundus photography, optical coherence tomography, fundus autofluorescence, fluorescein and indocyanine angiography, an electroretinogram and genetic testing. After determining the presence of secondary choroidal neovascularization, we treated her with intravitreal Ranibizumab injections. We present her progress and a brief literature review about ESCS. Results: An 11-year-old hyperopic female with no known family history of retinal disease or nyctalopia presented with bilateral reduced visual acuity (20/100 OD, 20/200 OS). Examination disclosed bilateral macular choroid neovascularization (CNV) with retinochoroidal anastomosis on the left eye, bilateral nummular deposits at the superior macular arcades. All three of her siblings, aged 7-14, were asymptomatic but were also hyperopic and had intraretinal schisis and focal loss or attenuation of the ellipsoid zone on optical coherence tomography (OCT). Electrophysiology showed a reduced scotopic response and a dramatically enhanced response to full field blue light stimuli meant to elicit a response primarily from S-cones. Genetic testing confirmed the presence of biallelic NR2E3 variants. Treatment with monthly intravitreal anti-VEGF resulted in improved visual acuity of 20/30 on the right eye, while the left eye had a persistent nodular scar and visual acuity remained at 20/200. Conclusion: We describe a case of bilateral CNV in a young patient with enhanced S-cone syndrome, discuss differentials and treatment approaches. This case highlights the risk of CNV in ESCS and the importance of family screening and follow-up in affected relatives.

Axis "microbiota – gut – eye": a review

Every organ in the human body has its own microbiota, and the eye, a complex multi-component organ, is no exception. Due to the limitations of traditional methods, detailed study of the ocular microbiome began only in 2010 as part of the Eye Microbiome Project, when advances in research methods made it possible to obtain detailed data, although there had been debate previously about whether microorganisms were even able to attach to the ocular surface due to the layers of the tear film, which have antibacterial properties. The cornea, conjunctiva, lacrimal glands and tear film, meibomian glands and microbiome form the microenvironment of the ocular surface, interacting together and resisting irritants, allergens and pathogens. Homeostasis of the ocular microbiota is critical for maintaining the health of the visual organ. Most microorganisms are found on the cornea and conjunctiva, and modern research methods, including 16S rRNA sequencing, have allowed us to establish the "core" of the ocular surface microbiota, identifying the most common types: Staphylococcus, Corynebacterium, Propionibacterium, and Streptococcus, although the exact composition of the “core” remains debatable. Many factors can influence the composition of the microbiome, including age, contact lens wear, ophthalmic medications, and antibiotics. Like the microbiome of many other organs, the ocular surface microbiome is influenced by the gut microbiome: this relationship has been called the "microbiota – gut – eye" axis. Within the "gut – eye" axis, healthy gut microbiota produce short-chain fatty acids, indoles, polyamines, and other substances that have a beneficial effect on the immune system and retinal health. The state of dysbiosis leads to disruption of homeostasis, and the increasing inflammatory reaction can contribute to damage to the optic nerve and progression of eye disease. Some ophthalmologic diseases, such as diabetic retinopathy, age-related macular degradation, choroidal neovascularization, uveitis, primary open-angle glaucoma, Sjogren's syndrome, dry eye syndrome are associated with dysbiosis of the intestinal microbial composition. Correction of intestinal dysbiosis using various methods can lead to a decrease in the risk of eye diseases, although additional research is needed to discover new methods for treating ophthalmologic pathologies along the "microbiota – gut – eye" axis.

Treatment Options in Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP): Case Presentation and Review of the Literature

ABSTRACT Purpose To outline the therapeutic approach for a rare case of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) and examine the current management recommendations of this uncommon condition. Methods-Results Literature review on the current treatment options in BDUMP cases. An 82-year-old woman was referred to our clinic due to bilateral visual loss. She was treated elsewhere with anti-vascular endothelial growth factors (anti-VEGF) in both eyes for presumed choroidal neovascularization (CNV) without improvement. Her past medical history (PMH) entailed colon cancer, treated with surgical resection and adjuvant chemotherapy 15 years ago. The patient presented with low visual acuity in both eyes, multiple oval orange patches in the fundus with striking hyperfluorescent pattern in fluorescein angiography (FA), giraffe pattern in fundus autofluorescence (FAF) and rapidly progressive cataracts. Intravitreal dexamethasone implants were administered with mild improvement and subretinal fluid absorption. Conclusions The management strategy in BDUMP should focus on the systemic, often occult malignancy. There is no standard treatment protocol for BDUMP; however, plasmapheresis in combination with primary malignancy treatment seems to yield promising results in current literature reports. Anti-VEGF injections failed to control BDUMP sequelae, however intravitreal dexamethasone implants may offer temporary relief.