Choroidal Neovascularization Research Articles

Targeting endothelial glycolytic reprogramming by tsRNA-1599 for ocular anti-angiogenesis therapy.

Rationale: Current treatments for ocular angiogenesis primarily focus on blocking the activity of vascular endothelial growth factor (VEGF), but unfavorable side effects and unsatisfactory efficacy remain issues. The identification of novel targets for anti-angiogenic treatment is still needed. Methods: We investigated the role of tsRNA-1599 in ocular angiogenesis using endothelial cells, a streptozotocin (STZ)-induced diabetic model, a laser-induced choroidal neovascularization model, and an oxygen-induced retinopathy model. CCK-8 assays, EdU assays, transwell assays, and matrigel assays were performed to assess the role of tsRNA-1599 in endothelial cells. Retinal digestion assays, Isolectin B4 (IB4) staining, and choroidal sprouting assays were conducted to evaluate the role of tsRNA-1599 in ocular angiogenesis. Transcriptomic analysis, metabolic analysis, RNA pull-down assays, and mass spectrometry were utilized to elucidate the mechanism underlying angiogenic effects mediated by tsRNA-1599. Results: tsRNA-1599 expression was up-regulated in experimental ocular angiogenesis models and endothelial cells in response to angiogenic stress. Silencing of tsRNA-1599 suppressed angiogenic effects in endothelial cells in vitro and inhibited pathological ocular angiogenesis in vivo. Mechanistically, tsRNA-1599 exhibited little effect on VEGF signaling but could cause reduced glycolysis and NAD+/NADH production in endothelial cells by regulating the expression of HK2 gene through interacting with YBX1, thus affecting endothelial effects. Conclusions: Targeting glycolytic reprogramming of endothelial cells by a tRNA-derived small RNA represents an exploitable therapeutic approach for ocular neovascular diseases.

Assessment of Choroidal Neovascular Membrane by Optical Coherence Tomography Angiography

Assessment of Choroidal Neovascular Membrane by Optical Coherence Tomography Angiography

Влияние осевой миопии на течение неоваскулярной формы возрастной макулярной дегенерации на фоне анти-VEGF-терапии

Purpose. To determine the effect of increased axial length of the eyes on the course of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD) during anti-VEGF therapy. Material and methods. The study included 29 people (34 eyes) with neovascular AMD occurring against the background of axial myopia, in comparison with control eyes. The length of the anterior-posterior axis (APA) was 25.42 (24.25; 27.55) mm. The influence of axial myopia on degenerative changes in the fundus such as myopic maculopathy and posterior staphyloma (PS) was analyzed. The type of CNV, parameters of the neovascular complex and retina, retinal microcirculation in the foveal area before treatment and at the end of the observation period, and correlations were assessed using optical coherence tomography (OCT) and OCT angiography (OCTA). Treatment was with intravitreal anti-VEGF. The follow-up period was 28.80 (15.18; 44.10) months. The number of intravitreal injections (IVI) was 7.75 (5.70; 9.85). Results. «Mild» categories of myopic maculopathy were detected by ophthalmoscopy – mosaic fundus (K1) in 20.60% and diffuse chorioretinal atrophy (K2) in 17.60% of cases. PS in eyes with CNV and fellow eyes was detected in 17.50 and 21.00% of eyes, respectively, types were identified exclusively without involvement of the macular area. CNV types 1 and 2 were detected in equal proportions – in 43.48 and 56.52% of eyes, respectively. Visual functions and OCT parameters of the retina and CNV reached the maximum positive values after 2 loading injections of anti-VEGF. A significant positive dynamics of retinal microcirculation in the foveal zone was established by the end of the observation period against the background of a decrease in exudative changes in the retina. Correlation analysis showed a direct relationship between the number of injections and the extent of CNV before treatment (rφ=0.743; p=0.009) and the height of the neuroepithelium above the CNV before treatment (r φ=0.378; p=0.027). Conclusion. The presence of axial myopia in patients with neovascular AMD contributes to the appearance of minimal degenerative changes in the posterior pole of the eyes, which has a positive effect on visual function and CNV during antiVEGF therapy. Key words: choroidal neovascularization, neovascular age-related macular degeneration, axial myopia, optical coherence tomography angiography, anti-VEGF therapy

ICG-based laser treatments for ophthalmic diseases: Toward their safe and rapid strategy.

The eye is a very important organ, and keratitis, corneal neovascularization, floaters, age-related macular degeneration, and other vision problems have seriously affected people's quality of life. Among the ophthalmic treatments, laser photocoagulations have been proposed and have shown therapeutic effects in clinical settings. However, corneal thinning and bleeding lesions induced by laser damage have led to limit its applications. To treat the issues of traditional hyperthermia treatments, photosensitizers [e.g., indocyanine green (ICG)] have been investigated to increase the therapeutic effects of corneal neovascularization and choroidal neovascularization. In the recent study, with the help of ICG, laser-induced nanobubble was proposed to treat vitreous opacities. The developed strategies could enlarge the effect of laser irradiation and reduce the side effects, so as to expand the scope of laser treatments in clinical ophthalmic diseases.

Effects of repeated intravitreal bevacizumab administration on anterior segment parameters and limbal stem cells

Background: Macular edema (ME) is fluid accumulation in the macula caused by vascular leakage. Repeated intravitreal bevacizumab (IVB) injections are extensively used to treat ME of different origins, are well tolerated, and have few side effects. This study evaluated the effects of repeated IVB injections on the anterior segment parameters and limbal stem cells (LSCs) in eyes with ME.
 Methods: This before–after study involved patients with ME of different causes who underwent repeated IVB injections at the Imam Khomeini Ophthalmology Center in Kermanshah, Iran. Before and after repeated IVB injections, anterior segment parameters were measured using anterior segment optical coherence tomography, and the LSCs were assessed using impression cytology.
 Results: We enrolled 42 eyes of 42 patients with a mean (standard deviation [SD]) age of 59.6 (7.6) years, of whom 25 (59.5%) were men and 17 (40.5%) were women. The underlying diseases included diabetic ME in 30 eyes (71.4%), central (5 [11.9%]) or branch (3 [7.1%]) retinal vein occlusion, and choroidal neovascularization in 4 eyes (9.5%). The right eye was affected in 22 (52.4%) participants. The mean (SD) number of IVB injections was 4.3 (1.3). After repeated injections, the mean central corneal thickness (CCT) increased, whereas the mean anterior chamber angle (ACA) and anterior chamber depth (ACD) decreased (all P<0.001). Three patients developed LSC deficiency after repeated IVB injections for diabetic ME.
 Conclusions: We observed a significant increase in the mean CCT and a decrease in the mean ACA and ACD after repeated IVB injections in our series. Three patients developed LSC deficiency after repeated IVB injections for diabetic ME management. The observed effect on LSC may cast doubt on the safety of repeated IVB injections; however, this finding must be verified in multicenter clinical trials with longer follow-up periods and larger study samples.

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.Graphical

Choroidal Nodules in Ocular Sarcoidosis.

Ocular sarcoidosis is present in 30-60% of all sarcoidosis patients. Our purpose is to increase awareness of the various presentations of ocular sarcoidosis. Short image-based clinical case report. We report on a case of ocular sarcoidosis presenting with unilateral choroidal nodules in a middle-aged man. Sarcoid uveitis is generally bilateral and rather symmetrical. However, choroidal nodules are an exception to this rule, as they generally arise unilaterally. Choroidal nodules are highly responsive to oral corticosteroids. When left untreated, they may evolve to chorioretinal atrophy and secondary choroidal neovascularization. Knowledge of this presentation of ocular sarcoidosis can help clinicians optimize treatment outcomes for patients.

Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.

Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota. Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice. Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV. These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.

Different approaches for treating myopic choroidal neovascularization: a network Meta-analysis.

To evaluate the efficacy of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF), photodynamic therapy (PDT), and laser treatment (LT) for anatomical and functional improvement in myopic choroidal neovascularization (mCNV) patients. Two researchers independently searched PubMed, Cochrane Library, Web of Science, and other databases to screen studies comparing best-corrected vision acuity (BCVA) and foveal center thickness (FCT) changes after mCNV treatment. Post-treatment chorioretinal atrophy (CRA) is a secondary outcome indicator. The retrieval time limit is from the database construction to January 30, 2023. A total of 1072 eyes in 16 articles were included. In the RCTs, intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) were superior to PDT (MD=0.18, 95%CI: 0.02, 0.40, MD=0.18, 95%CI: 0.01, 0.42) in improving BCVA of mCNV patients (P<0.05). The relative effectiveness in improving BCVA, from high to low, appeared to be IVR, intravitreal aflibercept (IVA), IVB, LT, PDT, and sham first followed by IVA (Sham/IVA). While improving the FCT from high to low was IVA, IVR, IVB, PDT. In retrospective studies, the results of BCVA after long-term treatment showed that all the therapeutic effects from high to low was IVA, intravitreal conbercept (IVC), IVR, IVB, IVB/IVR, PDT with IVB/IVR, PDT. The effect of improving FCT was IVA, IVR, IVC, PDT, and IVB from high to low. And in the effects of improving CRA, the IVB appeared to be higher than IVR, while the PDT was the smallest, but none of the differences in the results were statistically significant. Anti-VEGF has the best effect on long-term vision improvement in mCNV patients, using IVB or IVR alone to treat mCNV may be better than IVB or IVR combined with PDT. There is no significant difference in the improvement of visual acuity, macular edema, and CRA in mCNV patients treated with any different anti-VEGF drugs.

Clinical case of bilateral rapidly progressive osteoma of the choroid

Choroidal osteoma is a benign neoplasm characterized by the appearance of mature bone tissues at the level of the choroid and unilateral development. This study highlights a clinical case of bilateral rapidly progressing osteoma of the choroid in a child, which was complicated by tumor decalcification and choroidal neovascularization. A 14-year-old male teen has been under observation in the S. Fyodorov Eye Microsurgery Federal State Institution, Saint-Petersburg branch since 2019, for bilateral choroidal osteoma. At the initial visit, a yellow-orange lesion with clear boundaries was noted in the left eye, localized at the level of the choroid and parapapillary, and had a trabecular bone structure. Based on the clinical picture and data from instrumental studies (ultrasound and optical coherence tomography), he was diagnosed with choroidal osteoma. During observation, a similar lesion appeared in the right eye, and its relatively rapid growth was observed in both eyes. Owing to the absence of zones of decalcification and neovascularization, further follow-up was initiated. However, in the presence of zones of decalcification of the bone tissue and newly formed vessels of the choroid, a threefold intravitreal injection of an angiogenesis inhibitor was performed. Consequently, regression of choroidal neovascularization was observed. Speculatively, the main reason for the atypical disease course in this teenager is the specificity of bone tissue development in childhood and adolescence.

CHOROIDAL NEOVASCULARIZATION IN A CHILD WITH DOWN SYNDROME

Purpose: To report a case of Down syndrome with myopic choroidal neovascularization (CNV) and the treatment outcome. Methods: Case report. Main outcome measures include refractive error, fundus examination, optical coherence tomography (OCT), OCT angiography (OCTA), fluorescein angiography (FA), anti-vascular endothelial growth factor (VEGF) injections. Results: A 12-year-old boy with Down syndrome presented at a regular check-up with decreased visual acuity (VA) with macular degeneration in the left eye. The best-corrected VA was 0.6 in the right eye and 0.1 in the left eye, which decreased from 0.3 1 year ago. The refractive error (spherical equivalent) was -5.25 diopters (D) in the right eye and -8.00 D in the left eye. Detailed examinations were performed under general anesthesia. The fundus examination showed macular degeneration with retinal pigment epithelium (RPE) atrophy, pigmentary changes, and fibrous tissue in the left eye. OCT showed CNV at the macula with edema, and OCTA showed spreading CNV above the RPE at the macula in the left eye. FA showed hyperfluorescence in the early phase and late dye leakage from the CNV. Intravitreal ranibizumab injections were administered twice within 2 months, and he maintained a VA of 0.1 in the left eye. Conclusion: CNV and associated macular degeneration may occur in Down syndrome with high myopia possibly because of the abnormal choroidal structure. In children with Down syndrome, regular fundus examinations with OCT are important for early detection and treatment of CNV.

Crocetin inhibits choroidal neovascularization in both in vitro and in vivo models

Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1β, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.

The occurrence of age-related macular degeneration in the presence of a transferred, confirmed COVID-19

BACKGROUND: COVID-19 can affect the eyes and both the anterior and posterior segments of the eye. Retinal complications associated with COVID-19 have been reported.&#x0D; CLINICAL CASE DESCRIPTION: We present a clinical case of age-related macular degeneration that developed during the acute period of coronavirus infection. A patient with COVID-19 and pneumonia (CT-1) experienced sudden decrease in visual acuity within 1 month. A dark spot appeared in front of the left eye, which did not disappear despite eye movements, and distortion of objects was observed. The disease was manifested acutely. A complete ophthalmological examination revealed a sharp decrease in visual acuity and a positive Amsler test (distortion of lines at a distance of 30 cm). In the field of view, scotomas were noted in the center. Ophthalmoscopy revealed light and dark foci in the central macular zone of the retina. Cptical coherence tomography with an angiographic mode detected severe changes at the level of the neuroepithelium and retinal pigment epithelium with the formation of gray tissue. Aflibercept (approved for use in the Russian Federation, No. LP-003544) was intravitreally prescribed according to the clinical guidelines for treating age-related macular degeneration. After treatment with positive dynamics, visual acuity increased to 1.0, and the thickness of the retina decreased by 102 microns.&#x0D; CONCLUSION: The key objective in making a correct diagnosis was the use of optical coherence tomography with an angiographic mode. This method allows the visualization of the retinal layers without invasion The angiography mode allows the assessment of the state of the foveolar avascular zone and the density and perfusion of blood vessels, which enable the diagnosis of age-related macular degeneration and choroidal neovascularization. Timely antiangiogenic treatment, that is, a single intraocular injection, completely restored the visual acuity and visual field and normalized the state of the retina according to objective data of optical coherence tomography with angiography mode.

Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor

BackgroundPrevious studies on the biomarkers of pathologic myopia choroidal neovascularization (pmCNV) development merely detected limited types of proteins and provide a meagre illustration of the underlying pathways. Hence, a landscape of protein changes in the aqueous humor (AH) of pmCNV patients is lacking. Here, to explore the potential mechanisms and biomarkers of pmCNV, we analyzed the clinical data and protein profile among atrophic (A) lesions, tractional lesions (T) and neovascular (N) lesions in myopic patients based on the ATN grading system for myopic maculopathy (MM).ResultsAfter investigating demographic data of our patients, a correlation was found between A and N lesions (R = 0.5753, P < 0.0001). Accordingly, groups were divided into patients without MM, patients with myopic atrophic maculopathy (MAM), and patients with pmCNV (N2a lesion). In proteomics analysis, the increased protein level of GFAP and complement-associated molecules in AH samples of the 3 groups also indicated that MAM and pmCNV shared similar characteristics. The GO enrichment and KEGG pathway analysis were performed, which mapped that differential expressed proteins mainly engaged in JAK-STAT pathway between the pmCNV group and two controls. Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248.ConclusionsAtrophic lesions under pathologic myopic conditions demonstrated similarities to neovascularization development. Potential biomarkers including GFAP were associated with the pathogenesis of pmCNV. In summary, our study provides new insights for further research on pmCNV development.

Recent Advances in Imaging Macular Atrophy for Late-Stage Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD eventually results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicts advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus photography; dye-based angiography; fundus autofluorescence (FAF); near-infrared reflectance (NIR); optical coherence tomography (OCT); and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. These evolving diverse imaging modalities optimize detection of pathologic anatomy and measurement of visual function; they may also contribute to the understanding of underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

Minocycline and Diacetyl Minocycline Eye Drops Reduce Ocular Neovascularization in Mice.

To evaluate the efficacy of minocycline and a novel, modified minocycline analogue that lacks antimicrobial action, diacetyl minocycline (DAM), on choroidal neovascularization (CNV) in mice of both sexes. CNV was induced via laser injury in female and male C57BL/6J mice. Minocycline, DAM, or saline was administered via topical eye drops twice a day for 2 weeks starting the day after laser injury. CNV volume was measured using immunohistochemistry labeling and confocal microscopy. Minocycline reduced lesion volume by 79% (P ≤ 0.0004) in female and male mice. DAM reduced lesion volume by 73% (P ≤ 0.001) in female and male mice. There was no significant difference in lesion volume between minocycline and DAM treatment groups or between female and male mice. Both minocycline and DAM eye drops significantly reduced laser-induced CNV lesion volume in female and male mice. While oral tetracyclines have been shown to mitigate pathologic neovascularization in both preclinical studies and clinical trials, the present data are the first to suggest that tetracycline derivatives may be effective to reduce pathologic CNV when administered via topical eye drops. However, the action is unrelated to antimicrobial action. Targeted delivery of these medications via eye drops may reduce the potential for systemic side effects. Topical administration of minocycline and/or DAM via eye drops may represent a novel therapeutic strategy for disorders involving pathologic CNV.

Marine bromophenols suppressed choroidal neovascularization by targeting HUWE1 through NF-κb signaling pathway

Inflammation plays a key role in the progression of choroidal neovascularization (CNV). Regular intravitreal injection of anti-VEGF medication is required for many patients to sustain eye condition as CNV always recurs due to persistent chronic inflammation in the retina and choroid. Marine bromophenols (BDB) have been widely studied due to their diverse bioactivities, including anti-inflammatory effect, though the mechanism of which remained unclear. Our study demonstrated that BDB could restricted endothelial cells' function and suppressed choroidal explants both in vitro and in vivo without out affecting the cells viability. BDB also significantly reduced numerous inflammatory cytokines in both raw cells and choroidal tissue, including IL-1β, IL-6, TNF-α, IL-4 and MMP-9. Moreover, we demonstrated that BDB down regulated phosphorylation of NF-κB p65 in the raw cells. By Co-IP assay, HUWE1 was found to be bound with BDB and the binding location was at sequences position 4214. When overexpressed HUWE1 in HUVECs, the suppression of endothelial cells' function by BDB became more significant. Taken together, the findings in this study showed that BDB suppressed endothelial cells' function and choroidal neovascularization by targeting HUWE1 through NF-κB pathway, which suggested that BDB could be a potential therapeutic candidate in treating chronic inflammation in choroidal neovascularization.

ANATOMICAL AND FUNCTIONAL OUTCOMES OF BEVACIZUMAB TREATMENT IN PEDIATRIC AUTOSOMAL RECESSIVE BESTROPHINOPATHY.

The purpose of this study was to report functional and anatomical outcomes of anti-VEGF treatment in eyes with autosomal recessive bestrophinopathy (ARB) presenting in the first decade of life. The study included case series of four eyes from two siblings with compound heterozygous mutations in the BEST1 gene who were treated with eight monthly intravitreal bevacizumab injections. Response to treatment was analyzed using color fundus photography, fundus autofluorescence, optical coherence tomography, OCT angiography, and microperimetry. Patient 1 (male, age 9 years) had visual acuity of 20/20 in the right eye and 20/50 in the left eye. Patient 2 (female, age 10 years) had visual acuity of 20/25 in the right eye and 20/20 in the left eye. All eyes had multifocal subretinal deposition of lipofuscin and subretinal fluid, and three eyes had choroidal neovascularization (CNV). Lipofuscin material reabsorbed in 2 of 4 eyes, the CNV regressed in 3 of 3 eyes, a bacillary detachment resolved in 1 of 1 eye, but the subretinal fluid did not change. Functional improvement in visual acuity was noted, but MP showed scattered areas of reduced retinal sensitivity. No ocular or systemic side effects were detected. Anti-VEGF treatment of choroidal neovascularization in eyes with ARB resulted in anatomical changes that were only clinically significant in the eye with decreased visual acuity. The hyporeflective subretinal material remained unchanged suggesting a nonexudative cause. These findings provide new insights into the management of ARB, especially in pediatric subjects with CNV.

Preliminary analysis of predicting the first recurrence in patients with neovascular age-related macular degeneration using deep learning

BackgroundTo predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF).MethodsOptical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented.ResultsA total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20 ± 15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725 ± 0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence.ConclusionsThe deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.

Differential diagnosis of myopic choroidal neovascularization (mCNV): insights from multimodal imaging and treatment implications.

The aim of this article is to conduct a comprehensive systematic review about the current understandings and differential diagnosis of myopic choroidal neovascularization (mCNV) and other several similar diseases, describing their multimodal imaging analysis, prognostic implications, and current types of management. This systematic review was performed based on a search on the PubMed database of relevant papers regarding mCNV and other entities discussed in the paper, according to our current knowledge. Through the integration of a multimodal imaging approach, especially optical coherence tomography (OCT), along with accurate demographic and clinical assessment, it becomes possible to effectively differentiate mCNV from similar yet heterogeneous entities. These conditions include macular hemorrhage due to new lacquer crack (LC) formation, inflammatory diseases such as punctate inner choroidopathy (PIC)/multifocal choroidits (MFC) and epiphenomenon multiple evanescent white dot syndrome (Epi-MEWDS), neovascular age-related macular degeneration (nAMD), idiopathic CNV (ICNV), dome-shaped macula (DSM) with subretinal fluid, retinal pigment epithelium (RPE) humps, angioid streaks (AS), choroidal rupture (CR), and choroidal osteoma (CO). Each one of these entities will be described and discussed in this article. Myopic choroidal neovascularization is a common retinal condition, especially among young individuals. Accurate diagnosis and differentiation from similar conditions are crucial for effective treatment. Multimodal imaging, particularly OCT, plays a crucial role in precise assessment. Future research should focus on defining biomarkers and distinguishing features to facilitate prompt treatment.