Choroidal Neovascularization Research Articles

5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/β-Catenin Signaling Pathway.

Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.

From the Eye to the Heart: Association between Age-Related Macular Degeneration and Cardiovascular Disease (a Systematic Review)

Introduction & ObjectivesAge-related macular degeneration (AMD) is the third leading cause of global blindness, whilecardiovascular disease (CVD) is recognized as a major cause of morbidity and mortality. Both arecomplex diseases associated with aging. It has recently been argued that there is an associationbetween AMD and CVD. This study examined whether AMD increased the risk of CVD and/ or CVDmortality.
 MethodsA systematic review was conducted through three databases (Pubmed, Scopus, and Embase) forrelevant studies published between 2016-2023. We selected studies which focused on subjects withAMD, regardless of stages, and their risks for developing CVD and/or CVD mortality.
 ResultsTwo cohort studies and one case-control study are included, involving 93.388 patients aged >40years old. One cohort study found that subjects with choroidal neovascularization were associatedwith an increased rate of cardiovascular mortality (HR 3.16 95% CI 1.62-6.15). Another study alsofound that AMD was associated with a 1.58 fold increased risk of heart failure (adjusted OR, 1.56;95% CI, 1.16–1.87; P<0.001) after adjustment for confounders. Moreover, aside from the variableson which this systematic review focused on, the cohort studies also found AMD correlation withother diseases and causes of mortality.
 ConclusionIndividuals with AMD have higher risk for developing CVD. Thus, screening for AMD may bebeneficial in preventing CVD.

Classic Choroidal Neovascularization in Young Man

Introduction : Classic choroidal neovascularization (CNV 2) represent a pathological growth of blood vessels and can result in loss of visual function. The most common cause of CNV 2 in elderly patients is age- related macular degeneration, meanwhile in young age it is frequently due to inflammation, high myopia, angioid disks and hereditary disorders. Hence, the presented case reports the characteristic findings as well the management of the disease.
 Case Illustration : A 37-year-old man had two weeks history of metamorphopsia on both eyes. The left eye (LE) had a worse visual acuity, macular fibrosis with pigment epithelial detachment in funduscopy and Optical Coherence Tomography (OCT). A submacular hemorrhage and exudative lesion were recognized on the right eye (RE) with type 2 choroidal neovascularization. Fundus Fluorescence Angiography (FFA) was also performed. Systemic conditions were unremarkable. Intravitreal anti-VEGF injections on RE were given for three consecutive months and showed significant improvement.
 Discussion : The etiology of CNV 2 includes high myopia, and inflammation. However, none was found in this patient. Nonetheless, CNV type 2 is still uncommon in young age without predisposing conditions. As most common lesions involve the macula, symptoms shown include metamorphopsia, central scotoma and floaters. FFA is still considered to be the gold standard to differentiate the types of choroidal vascularization. Neovascularization and submacular hemorrhage can be treated with intravitreal injection of anti-VEGF, as previous studies reported significant improvement.
 Conclusion : This was a case of bilateral CNV type 2 in a young man without any previous predisposing conditions. Three monthly injections of anti-VEGF showed significant improvement.

SERIAL CASES INTRAVITREAL TENECTEPLASE AND PNEUMATIC DISPLACEMENT OF SUBMACULAR HEMORRHAGE

Introduction : OBJECTIVE Submacular hemorrhage {SMH} is uncommon complication of choroidal or retinal vascular abnormalities, including choroidal neovascularization {CNV}, polypoidal choroidal vasculopathy {PCV} and retinal macroaneurysm of these, PCV is condition most frequency associated with large SMH {reported in 20%-63% of eyes with PCV} PURPOSE To presence successful management of submacular hemorrhage with combination injection intravitreal {IVT} Tenecteplase and gas C3F8 100%
 Case Illustration : METHODES All patient with SMH already take foto fundus and OCT pre and post IVT methalyse and gas C3F8 100%. All patients undergone IVT gas C3F8 100% 0.2 cc and take a rest for 20 second after that IVT methalyse 0.1 cc was injected. Positioning 1st 24 hours: Free Positioning, 2nd 24 hour: Positioned face down, 3rd days: Follow up.
 Discussion : RESULT The submacular hemorrhage move out from macular for all of cases. Vision improvement occourred in all cases.
 Conclusion : CONCLUTION Intravitreal Tenecteplase in conjunction with pneumatic displacement appears effective in displacing submacular blood.

THE OUTCOME OF INTRAVITREAL BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATMENT

Introduction : Age-related macular degeneration (AMD) is a disease that results in irreversible severe loss of central vision in people over 50 years old. Hence, anti-VEGF therapy has become a standard treatment for neovascular AMD. Brolucizumab is a single-chain antibody fragment that inhibits VEGF-A binding to VEGF receptors. It has a higher molar concentration that allows a greater reduction in the central subfield thickness (CST)
 Case Illustration : A 59-year-old male with a chief complaint of gradually blurred vision in the left eye for 2 years. BCVA of the left eye was 0.3, OCT showed a hyperreflective band in the sub-neurosensory space with subretinal fluid in the left eye (Figure 1), and OCT-A revealed choroidal neovascularization (Figure 2). The patient was diagnosed with AMD AREDS IV in the left eye. He had undergone three monthly injections of brolucizumab. BCVA of the left eye after injection improved to 1.0 and OCT imaging showed no subretinal fluid, no intraretinal fluid, and no pigment epithelial detachment.
 Discussion : Brolucizumab has a greater reduction in CST because of its high molecular concentration. Results of HAWK and HARRIER concluded that brolucizumab was non-inferior towards aflibercept in BCVA change at week 48. According to the HAWK trial, a greater reduction of CST was seen in week 16 among eyes treated with brolucizumab. Brolucizumab was also well tolerated and adverse event rates were similar to aflibercept.
 Conclusion : Brolucizumab could be an alternative treatment option considering its efficacy in improving visual acuity and reducing CST.

Myopic choroidal neovascularization with neovascular signal around perforating scleral vessel prone to recur after anti-VEGF therapy

BackgroundTo compare the recurrence of myopic choroidal neovascularization (mCNV) based on the neovascular signal of mCNV around the perforating scleral vessel (PSV).MethodsA consecutive series of naïve patients with mCNV accepted anti-VEGF therapy with a minimum 12-month follow-up period. The neovascular signal relationship between PSV and mCNV were classified into the presence of neovascular signal of CNV around PSV or not. The recurrence of mCNV, best-corrected visual acuity (BCVA), hyperreflective foci height, CNV area and CNV flow area were analyzed between two groups.ResultsNeovascular signal of CNV around PSV was detected in 20 eyes (39.2%). The one-year recurrence rate in the group with neovascular signal of CNV around PSV was significantly higher than that in the group without neovascular signal of CNV around PSV (P = 0.045). The recurrence time in the group with neovascular signal around PSV was shorter than that in the group without neovascular signal around PSV (P = 0.030). Cox proportional hazard model showed that the presence of neovascular signal of CNV around PSV [hazard ratio (HR): 2.904] and subfoveal choroidal thickness ≤ 50 μm (HR: 0.368) were risk factors for recurrence of mCNV. In the group with neovascular signal around PSV, the BCVA was worse (P = 0.024) and the CNV flow area was more unstable (P = 0.027) after therapy.ConclusionsPSV was commonly detected in patients with mCNV. The presence of neovascular signal of CNV around PSV was prone to recur with a shorter time in mCNV patients.

Progression of retinal choroidal neovascularizationby latent human cytomegalovirus infection and immunological signaling among neonatal patients admitted to tertiary care hospital.

Choroidal neovascularization (CNV) is a serious condition that affects the retina, causing partial or complete blindness in people of different ages. While CNV is a common occurrence in various chorioretinopathies, research on its occurrence in neonates is limited. Human cytomegalovirus (HCMV) is a significant health threat to neonates, with a strong association with retinal angiogenesis. However, there has been limited investigation into HCMV-associated CNV progression. In this article, we extensively studied the expression of different inflammatory cytokines and chemokines during latent HCMV-associated retinal neovascularization. Our research found that HCMV-induced CNV progression was significantly prominent in the presence of AT2R-dependent angiogenesis (p < 0.001), whereas in the absence of HCMV, AT1R-dependent CCL-5-mediated angiogenesis was documented. We also observed significant increases in CCL-19, CCL-21 chemokine responses, followed by CCR-7 chemokine receptor activation (p < 0.001) in HCMV-induced CNV patients compared to HCMV non-induced CNV groups. Furthermore, significant changes in predictive chemokine markers of HCMV-induced CNV were positively correlated with HCMV viremia. These immunological alterations ultimately lead to the switching of NFκB canonical and noncanonical pathways, respectively, in HCMV-induced neonatal CNV and HCMV non-induced CNV. This clinical observation presents a novel hypothesis that ocular HCMV latency poses a noteworthy risk factor for the progression of retinal neovascularization through a distinctive immunological signaling pathway. The current study represents the first of its kind to report on this association, which may have significant implications for the clinical management of patients with ocular HCMV.

CRISPR‐based gene therapy for wet age‐related macular degeneration in mouse model

AbstractWet age‐related macular degeneration (AMD) is a common cause of vision loss in the elderly. It is characterised by choroidal neovascularisation (CNV), caused by overexpression of vascular endothelial growth factor (VEGF), resulting in abnormal vessel proliferation. Current clinical management predominantly relies on anti‐VEGF agents, which require frequent and costly injections. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has emerged as a promising strategy for permanently suppressing angiogenesis by targeting the VEGF‐related pathway. Increased research suggests that disrupting this pathway holds potential for preventing CNV progression. This review provides an overview of the aetiology, classification and pathophysiology of wet AMD, followed by a concise summary of current gene editing research using the CRISPR/Cas system via viral vector delivery strategies to target ocular pro‐angiogenic factors, including Hif‐1α, VEGF and VEGFR. The importance of timely targeting of VEGFA is emphasised and the challenges associated with gene editing therapies are also highlighted.

Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS® Registry Analysis.

This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS® Registry. This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed. The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion. In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:220-226.].

Assistance Burden Comparison Between Age-Related Macular Degeneration and Retinal Angiomatous Proliferation Over a Three-Year Follow-up.

We compared assistance burden between neovascular age-related macular degeneration (nAMD) and retinal angiomatous proliferation (RAP) under intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment on a treat-and-extend (T&E) regimen in a third-level hospital in a developed country. This retrospective study using data from the Fight Retinal Blindness! Registry included patients treated between January 2016 and December 2020. Final event was established as best corrected visual acuity (BCVA) lower than 20 Early Treatment Diabetic Retinopathy Study letters. According to choroidal neovascularization (CNV), three different study groups were established: type 1, 2, and 3. A total of 285 eyes of 227 patients were included. Mean age was 80.1 ± 6.5, 79.1 ± 7.9, and 81.2 ± 7.2 years, for the three study groups, respectively. Mean injections were 16.0 ± 4.8, 16.5 ± 4.1, and 14.1 ± 5.7, respectively; and mean number of visits were 17.9 ± 4.3, 18.2 ± 3.1, and 16.8 ± 5.3, respectively. No differences were found (P > 0.05). Survival curves and log-rank analysis also showed no differences (P = 0.344). Cox proportional hazard models showed that a lower baseline BCVA, subfoveal geographic atrophy (GA), and subfoveal fibrosis (SF) were associated with a higher risk of reaching ≤ 20 letters. nAMD and RAP under a T&E regimen indicate a high assistance burden during the first three years. The presence of subfoveal GA or SF are associated with a BCVA lower than 20 letters. [Ophthalmic Surg Lasers Imaging Retina 2024;55:197-203.].

Topical Ophthalmic Liposomes Dual-Modified with Penetratin and Hyaluronic Acid for the Noninvasive Treatment of Neovascular Age-Related Macular Degeneration.

Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.

Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration

ObjectiveTo assess the non-inferiority of biosimilar aflibercept (CinnaGen Company, Iran) (P041) to the originator aflibercept (Regeneron, US) (AFL) in terms of efficacy, safety, and immunogenicity. DesignThis was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SubjectsPatients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the two groups of P041 and AFL. Methods and InterventionsPatients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. Main Outcome MeasuresThe primary outcome was the non-inferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity (VA) and retinal thickness, safety evaluation, and immunogenicity during the study. ResultsIn total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in P041 compared to 94.52% in AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined non-inferiority margin of 10% (p-value: 0.98, 95% CI, -0.0008 (-0.074, 0.074)). Secondary outcomes indicated similar results in both arms (all p-values >0.05). Safety measured outcomes and immunogenicity were similar between the two study groups. ConclusionP041 was noninferior to AFL in eyes with n-AMD. Other efficacy and safety findings also indicated the similarity of two products.

Calcified Sclero-Choroidal Choristomas in Mosaic RASopathies: A Description of a New Imaging Sign

PurposeTo evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of mosaic RASopathy patients. DesignSingle-center retrospective observational study. SubjectsTen eyes with calcified fundus lesions in 7 mosaic RASopathy patients. MethodsThe lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) scan where available. Main Outcome MeasuresThe imaging characteristics of calcified fundus lesions were assessed. ResultsWe found seven patients with mosaic RASopathies, 5 males and 2 females (3 with Linear Sebaceous Nevus Syndrome, 3 with Oculoectodermal Syndrome, and 1 with Encephalocraniocutaneous Lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but two of these lesions involved both the choroid and sclera, with two of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane (CNV) necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan and all four showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, one had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. ConclusionsWe propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas (CaSCCs) and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen.

Efficacy and safety of intravitreal faricimab for neovascular age-related macular degeneration: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (− 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = − 5.96; 95% CI = (− 7.11, − 4.82)], total CNV area [WMD = − 0.49; 95% CI = (− 0.68, − 0.30)], and total lesion leakage [WMD = − 0.88; 95% CI = (− 1.08, − 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).

Type 1 and type 2 torpedo maculopathy.

To analyze torpedo maculopathy (TM) and to report the characteristics of the disease. Retrospective study. The review of a database for clinical diagnosis identified eight patients with TM lesions in the retina between 2016 and 2022. Multimodal imaging was used to analyze the cases. All cases were unilateral, asymptomatic, and hypopigmented. They were associated by surrounding hyperpigmented retinal pigment epithelium changes to varying degrees. All lesions were located in the temporal retina on the horizontal axis, pointing towards the fovea, except for one patient with a lesion inferior to the fovea. Optical coherence tomography imaging revealed a normal inner retina in all eyes. In the area of the TM lesion, attenuation of the interdigitation zone was seen in mild cases (three cases). All other five patients had thinning of the outer nuclear layer and loss of ellipsoid zone and interdigitation zone of the TM lesion. Four of these cases had a subretinal cavitation/cleft, and two of them additionally an inner choroidal excavation. No patient had any sign of choroidal neovascularization. The average age for patients with type 1 TM was 18years and for type 2 TM 16.5years. In this large case series, we could not detect an age difference between the different types of the TM. Contrary to previous discussions, type 2 TM can also occur in young patients.

Best Vitelliform Macular Dystrophy Natural History Study Report 1: Clinical Features and Genetic Findings

To analyze the genetic findings, clinical spectrum, and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults. Single-center retrospective, consecutive, observational study. Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene. Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed. Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters. Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3-84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti-vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His). BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sulfated CXCR3 Peptide Trap Use as a Promising Therapeutic Approach for Age-Related Macular Degeneration.

Chemokines have various biological functions and potential roles in the development or progression of neuroinflammatory diseases. However, the specific pathogenic roles of chemokines in the major cause for vision loss among the elderly, the leading cause of blindness in older individuals, remain elusive. Chemokines interact with their receptors expressed in the endothelium and on leukocytes. The sulfation of tyrosine residues in chemokine receptors increases the strength of ligand-receptor interaction and modulates signaling. Therefore, in the present study, we aimed to construct a human recombinant sulfated CXCR3 peptide trap (hCXCR3-S2) and mouse recombinant sulfated CXCR3 peptide trap (mCXCR3-S2) to demonstrate in vivo effects in preventing choroidal neovascularization (CNV) and chemotaxis. We generated expression vectors for mCXCR3-S2 and hCXCR3-S2 with GST domains and their respective cDNA sequences. Following overexpression in E. coli BL21 (DE3), we purified the fusion proteins from cell lysates using affinity chromatography. First, the impact of hCXCR3-S2 was validated in vitro. Subsequently, the in vivo efficacy of mCXCR3-S2 was investigated using a laser-induced CNV mouse model, a mouse model of neovascular age-related macular degeneration (AMD). hCXCR3-S2 inhibited the migration and invasion of two human cancer cell lines. Intravitreal injection of mCXCR3-S2 attenuated CNV and macrophage recruitment in neovascular lesions of mouse models. These in vitro and in vivo effects were significantly stronger with CXCR3-S2 than with wild-type CXCR3 peptides. These findings demonstrate that the sulfated form of the CXCR3 peptide trap is a valuable tool that could be supplemented with antivascular endothelial growth factors in AMD treatment.

Deep learning-based classification of eye diseases using Convolutional Neural Network for OCT images

Deep learning shows promising results in extracting useful information from medical images. The proposed work applies a Convolutional Neural Network (CNN) on retinal images to extract features that allow early detection of ophthalmic diseases. Early disease diagnosis is critical to retinal treatment. Any damage that occurs to retinal tissues that cannot be recovered can result in permanent degradation or even complete loss of sight. The proposed deep-learning algorithm detects three different diseases from features extracted from Optical Coherence Tomography (OCT) images. The deep-learning algorithm uses CNN to classify OCT images into four categories. The four categories are Normal retina, Diabetic Macular Edema (DME), Choroidal Neovascular Membranes (CNM), and Age-related Macular Degeneration (AMD). The proposed work uses publicly available OCT retinal images as a dataset. The experimental results show significant enhancement in classification accuracy while detecting the features of the three listed diseases.

Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration

Age-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)+ splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1+ splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.

Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis

To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. Multicenter retrospective matched cohort study. Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.