Neovascular Macular Degeneration Research Articles

Full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration.

To describe a case of full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration, which has not been reported to date. A 65-year-old male patient received brolucizumab intravitreal injection therapy for neovascular macular degeneration of the right eye. He received multiple intravitreal anti-VEGF injections on a pro re nata regimen and developed a full thickness macular hole. Surgical treatment was performed with pars plana vitrectomy of the right eye. Full thickness macular hole was successfully treated. Although a full thickness macular hole following intravitreal brolucizumab injection is an uncommon complication, it requires caution.

Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr−/− mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFβ2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFβ receptor I/II complex by interacting with unglycosylated TGFβ receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFβ2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.

How Advanced are Nanocarriers for Effective Subretinal Injection?

Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt's disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber's congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber's congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.

Fibrosis in age-related neovascular macular degeneration in the anti-VEGF era.

The natural history of neovascular age-related macular degeneration (nAMD) leads to scarring and loss of vision. Since the advent of anti-VEGF therapies, which are very effective for controlling exudation, large disciform scars are rarely encountered in the clinic. However long term studies show that smaller and less severe fibrotic scars are not uncommon and develop over time despite optimal treatment. This means that additional mechanisms of action may be required to completely address this condition. To permit new treatments, a proper understanding of the clinical impact of fibrosis is required. This review is focused on clinical aspects of fibrosis and summarises recent data on biomarkers, prevalence, causes, consequences, and therapies, highlighting the most important and urgent topics to tackle in order to advance in the treatment of fibrosis.

Анализ ОКТ-предикторов анатомических и функциональных результатов aнтиангиогенной терапии отслойки пигментного эпителия при неоваскулярной возрастной макулярной дегенерации

Abstract Analysis of OCT predictors of anatomical and functional results of anti-VEGF therapy of pigment epithelium detachment in neovascular age-related macular degeneration E.V. Kozina, S.N. Sakhnov, V.V. Myasnikova, E.V. Bykova S. Fyodorov Eye Microsurgery Federal State Institution, Krasnodar branch, Krasnodar, Russian Federation Kuban State Medical University Ministry of Health of Russia, Krasnodar, Russian Federation Purpose. Analysis of optical coherence tomography (OCT) biomarkers for anatomical results prediction of anti-angiogenic therapy (antiVEGF) of pigment epithelial detachments (PED) in neovascular macular degeneration (n-AMD). Material and methods. Primary tomograms of 260 patients with PED higher than 200 µm were analyzed. The shape, height, length of the detachment and subpigmentary space reflectivity were assessed. After anti-VEGF injections, reattachment of PED according to OCT was observed in 114cases (44%) – 1st group; in 111 cases (43%) OCT showed PED resistance – 2nd group; in 35 cases (13%), the pigment epithelium tear (RPET) of 3–4 degrees was happened – 3rd group. In each OCT were studied of the following biomarkers: the ellipsoidal zone and RPE integrity, intra – and subretinal fluid, the drusen under RPE around PED, hyperreflective foci in retina. Results. A statistically significant difference was revealed between 1st and 2nd groups in the height and length of pigment epithelium detachment: PED height (506.2±204.3 µm) and length (3206.2±722.1 µm) have a tendency to reattachment during anti-VEGF therapy (р<0.05). High PED with neuroepithelial detachment has a higher risk of RPET (р<0.05). Presence of RPE defects and large hyperreflective foci in the retina can be considered as a predictor of the PED reattachment (р<0.05). Low PED with reflectivity subpigmentary space is a predictor of PED resistance (р<0.05). Conclusion. Patients with high PED, with neuroepithelial detachment, should be given antiVEGF therapy with great caution. Lower PED with hyperreflectity under PED tend to be anatomically resistant to therapy. Biomarkers of the adherence of the PE can be RPE defects and large hyperreflective inclusions in the internal layers. Key words: retinal pigment epithelium detachment, pigment epithelium tear, OCT biomarkers, hyperreflective foci, antiangiogenic therapy

Verteporfin regulates corneal neovascularization through inhibition of YAP protein activation

Corneal neovascularization (CNV) is a vision-threatening disease that is becoming a growing public health concern. While Yes-associated protein (YAP) plays a critical role in neovascular disease and allow for the sprouting angiogenesis. Verteporfin (VP) is a classical inhibitor of the YAP-TEAD complex, which is used for clinical treatment of neovascular macular degeneration through photodynamic therapy. The purpose of this study is to explore the effect of verteporfin (VP) on the inhibition of CNV and its potential mechanism. Rat CNV model were established by suturing in the central cornea and randomly divided into three groups (control, CNV and VP group). Neovascularization was observed by slit lamp to extend along the corneal limbus to the suture line. RNA-sequencing was used to reveal the related pathways on the CNV and the results revealed the vasculature development process and genes related with angiogenesis in CNV. In CNV group, we detected the nuclear translocation of YAP and the expression of CD31 in corneal neovascular endothelial cells through immunofluorescence. After the application of VP, the proliferation, migration and the tube formation of HUVECs were significantly inhibited. Furthermore, VP showed the CNV inhibition by tail vein injection without photoactivation. Then we found that the expression of phosphorylated YAP significantly decreased, and its downstream target protein connective tissue growth factor (CTGF) increased in the CNV group, while the expression was just opposite in other groups. Besides, both the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and cofilin significantly increased in CNV group, and decreased after VP treatment. Therefore, we conclude that Verteporfin could significantly inhibited the CNV without photoactivation by regulating the activation of YAP.

Integrative metabolome and lipidome analyses of plasma in neovascular macular degeneration

Age-related macular degeneration (AMD) causes irreversible vision-loss among the elderly in industrial countries. Neovascular AMD (nAMD), which refers to late-stage AMD, is characterized by severe vision-threatening choroidal neovascularization (CNV). Herein, we constructed a global metabolic network of nAMD, based on untargeted metabolomic and lipidomic analysis of plasma samples collected from sixty subjects (30 nAMD patients and 30 age-matched controls). Among the nAMD and control groups, 62 and 44 significantly different metabolites were detected in the positive and negative ion modes, respectively. Grouping analysis further showed that lipid and lipid-like molecule-based superclasses contained the highest number of significantly different metabolites. Lipidomic analysis revealed that 53 lipids among the nAMD and control groups differed significantly; these belonged to four major lipid categories (glycerophospholipids, sphingolipids, glycerolipids, and fatty acids). A discriminative biomarker panel comprising 16 metabolites and lipids, which was constructed using multivariate statistical machine learning methods, could effectively identify nAMD cases. Among these 16 compounds, eight were lipids that belonged to three lipid categories (glycerophospholipids, sphingolipids, and prenol lipids). The top three biomarkers with the highest importance scores were all lipids (a glycerophospholipid and two sphingolipids), highlighting the crucial role played by glycerophospholipid and sphingolipid pathways in nAMD. These differences between the metabolic and lipid profiles of nAMD patients and elderly individuals without AMD provide a readout of the overall metabolic status of nAMD. Further insights into the identified discriminative biomarkers may pave the way for future diagnostic and therapeutic interventions for nAMD.

Clinical outcomes in neovascular age-related macular degeneration: a cohort study of patients with care delay due to the COVID-19 pandemic

The COVID-19 pandemic has led to both intentional and unintentional care delay among age-related neovascular macular degeneration (nvAMD) patients. Prior studies have demonstrated that patients who discontinue nvAMD treatment for prolonged intervals are at high risk for vision loss, but less is known regarding shorter-term delay, such as during the height of the pandemic. Previous studies have looked at COVID-19 related delay in care and have shown a loss of visual acuity (VA) among these patients, but studies are limited by short follow-up or insufficient comparisons. This was an observational cohort study of nvAMD patients from March 1, 2019, through July 1, 2021, who experienced care delay. VA was modeled using a linear longitudinal mixed-effects model comparing historic data pre-lockdown to data post-lockdown. Covariates included baseline anatomic variables, demographic variables, and time intervals (treatment interval, delay interval). Secondary anatomic and treatment outcomes were modeled using a multilevel binary logistic regression model. 163 eyes among 116 patients were included. Initial longitudinal mixed-effects models found that although overall VA decreased at a yearly rate, when comparing pre-lockdown and post-lockdown time periods, VA slopes were not statistically different. Single-covariate longitudinal models showed that age, sex, and delay interval significantly affected VA slope. The multivariate longitudinal model found that a longer delay interval significantly decreased rate of VA loss. Multilevel binary logistic regression models showed a significant increase in odds of anti-VEGF treatment, presence of subretinal fluid, and macular hemorrhages in the post-lockdown period. Overall, when compared to historic data, rate of VA loss among our cohort did not vary significantly in pre-versus post-lockdown time periods, although treatment and anatomic variables did worsen post-lockdown suggesting that patients may be appropriately delayed but this comes at the risk of increased need for treatment.

Faricimab in neovascular AMD: first report of real-world outcomes in an independent retina clinic.

Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab. Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-naïve patients and non-naïve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded. Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612 ± 0.75 logMAR and 256.16 ± 12.98 µm respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387 ± 0.54 logMAR, as well as CRT values which decreased to 245.43 ± 15.34 µm. In the 3 naïve patients, mean baseline BVCA and CRT values were 0.33 ± 0.29 and 874.67 ± 510.86 µm, respectively. At one month follow-up, mean BCVA improved to 0.30 ± 0.29 logMAR and mean CRT was 536.04 ± 36.15 µm. Overall, a significant improvement in BCVA of 0.21 ± 41 logMAR and 238.44 ± 114.9 µm was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed. Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.

Pharmacokinetic evaluation of radiolabeled intraocular anti-CLEC14a antibody in preclinical animal species and application in humans.

Anti-angiogenic antibodies are widely used in the treatment of neovascular macular degeneration. Human antibody targeting C-type lectin domain family 14 member A (CLEC14a) is potential therapeutic agents owing to its antiangiogenic activity. In the present study, we aimed to predict the human intraocular pharmacokinetic (PK) properties of an anti-CLEC14a antibody. I-125 labeled aflibercept and anti-CLEC14a antibody were intravitreally injected into mice, rats, and rabbits. Single photon emission computed tomography/computed tomography imaging was performed, and the intraocular radioactivity concentration (%ID/ml) was obtained. The PK parameters in those three animal species were obtained by compartmental analysis. The PK parameters in humans were estimated by allometric scaling of the animal PK parameters with consideration of the hydrodynamic radius of the antibody. The mean half-life values of intraocular I-125-labeled aflibercept in mice, rats, and rabbits were 1.13 days, 1.25 days, and 4.91 days, respectively, by analysis with a one-compartment model. The predicted human half-life of intraocular aflibercept was 5.75 days based on vitreal volume by allometric scaling. The half-life values of intraocular I-125-labeled anti-CLEC14a in mice, rats and rabbits were 1.05 days, 1.84 days, and 6.37 days, respectively, by analysis with a one-compartment model. The predicted human half-life of intraocular anti-CLEC14a was 10.29 days based on vitreal volume. According to the hydrodynamic volume of the anti-CLEC14a, the predicted human half-life of intraocular anti-CLEC14a was 9.81 days. The PK characteristics of the intraocular anti-CLEC14a antibody were evaluated noninvasively in animals using I-125 labeling, and the intraocular PK characteristics in humans were predicted using these animal data. This methodology can be applied for the development of new antiangiogenic antibodies to treat macular degeneration.

Emotional and physical experiences of people with neovascular age-related macular degeneration during the injection process in Germany: a qualitative study

ObjectivesIn order to better understand the continued barriers to the provision of vascular endothelial inhibitor therapy, this study aims to investigate patients’ experiences with neovascular age-related macular degeneration (nvAMD) in...

Post-intravitreal Injection Endophthalmitis Identified with Point-of-care Ultrasound.

Case PresentationAn 88-year-old female presented to the emergency department (ED) with complaints of painful vision loss four days after an intravitreal injection for her neovascular macular degeneration. Her right eye visual acuity was markedly diminished with an absence of red reflex. A point-of-care ocular ultrasound was performed and demonstrated hyperechoic vitreous debris concerning for endophthalmitis.DiscussionEndophthalmitis is an infection of the vitreous or aqueous humors commonly caused by exogenous sources, such as inoculation of bacteria into the eye from surgery, injections, or trauma. It is an ophthalmologic emergency as it is a vision-threatening infection. Although a rare complication, post-surgery or post-injection are the leading causes of endophthalmitis. Point-of-care ocular ultrasound findings suggestive of endophthalmitis, such as hyperechoic vitreous debris, aid in the timely diagnosis and treatment of patients in the ED.

Choroidal endothelial and macrophage gene expression in atrophic and neovascular macular degeneration.

The human choroid is a heterogeneous, highly vascular connective tissue that dysfunctions in age-related macular degeneration (AMD). In this study, we performed single-cell RNA sequencing on 21 human choroids, 11 of which were derived from donors with early atrophic or neovascular AMD. Using this large donor cohort, we identified new gene expression signatures and immunohistochemically characterized discrete populations of resident macrophages, monocytes/inflammatory macrophages and dendritic cells. These three immune populations demonstrated unique expression patterns for AMD genetic risk factors, with dendritic cells possessing the highest expression of the neovascular AMD-associated MMP9 gene. Additionally, we performed trajectory analysis to model transcriptomic changes across the choroidal vasculature, and we identified expression signatures for endothelial cells from choroidal arterioles and venules. Finally, we performed differential expression analysis between control, early atrophic AMD, and neovascular AMD samples, and we observed that early atrophic AMD samples had high expression of SPARCL1, a gene that has been shown to increase in response to endothelial damage. Likewise, neovascular endothelial cells harbored gene expression changes consistent with endothelial cell damage and demonstrated increased expression of the sialomucins CD34 and ENCM, which were also observed at the protein level within neovascular membranes. Overall, this study characterizes the molecular features of new populations of choroidal endothelial cells and mononuclear phagocytes in a large cohort of AMD and control human donors.

Non-invasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults: EDNA diagnostic accuracy study.

Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear. The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration. This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used. This took place in hospital eye services. Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters. The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography. The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years. In total, 552 out of 578 patients who consented from 24 NHS hospitals (n = 16 ineligible; n = 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy [sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval)] was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9)], fundus clinical examination [53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9)], Amsler [33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5)], visual acuity [30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1)] and self-reported vision [4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5)]. Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities [c-statistic 0.66 (95% confidence interval 0.62 to 0.71)]. Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored. The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance. Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye. Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes. This study was registered as ISRCTN48855678. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.

Histology of neovascular myopic macular degeneration

To assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24–89 years; axial length: 25.5 ± 3.1 mm; range: 20–37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0–31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch’s membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P < 0.001), while the association with axial length was not significant (P = 0.43) in that model. After adjustment for the presence of macular BM defects, the nMMD prevalence was not associated with BM thickness (measured at the posterior pole, equator-posterior pole midpoint, equator and shortly posterior to the ora serrata) (P = 0.10; P = 0.87; P = 0.40; and P = 0.36, respectively), RPE cell layer thickness (P = 0.83; P = 0.79; P = 0.31; P = 0.38, resp.), RPE cell density (P = 0.56; P = 0.91; P = 0.47; P = 0.87, resp.), choriocapillaris thickness (P = 0.47; P = 0.93; P = 0.41; P = 0.75, resp.), and choriocapillaris density (P = 0.99; P = 0.94; P = 0.17; P = 0.97, resp.). The results suggest that nMMD is characterized by a fibrous pseudo-metaplasia of the RPE and is strongly associated with macular BM defects, without other detected histomorphometric differences in thickness or density of the RPE, BM, and choriocapillaris.

Comparing Effectiveness of Three Different Anti-VEGF Treatment Regimens for Neovascular Age-Related Macular Degeneration: Two Years' Real-World Clinical Outcomes.

PurposeTo compare and report the 2-year treatment outcomes from 3 different anti-VEGF treatment regimens in treating neovascular aged-related macular degeneration (nAMD): Ranibizumab pro re nata (Ranibizumab-PRN); Ranibizumab treat and extend (Ranibizumab-T&E); Aflibercept fixed first year dosing (7 injections) with treat and extend in subsequent year (Aflibercept-Fixed).MethodsAll treatment-naïve nAMD patients who completed 24 months of monitoring from a single treatment center were included. Patients received the initial loading dose of three injections (4-weekly interval), followed by one of the 3 treatment regimens. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcome was number of injections required in each year. Data analysis included last observation carried forward (LOCF) for patients with incomplete year-2 follow-up.ResultsA total of 249 eyes (230 patients) were studied: 121 Ranibizumab-PRN; 65 Ranibizumab-T&E, and 63 Aflibercept-Fixed. Baseline median VA (ETDRS letters) for Ranibizumab-PRN, Ranibizumab-T&E, and Aflibercept-Fixed was 53.9, 61.1, and 54.9 letters, achieving final VA of 54.9, 65.1, and 65.1 letters, respectively. Hence, the number of letters increased at the end of 24 months for each group was +1.0 (Ranibizumab-PRN), +4.0 (Ranibizumab-T&E), highest +10.2 in Aflibercept-Fixed group. Median number of injections over 2 years (year-1/year-2) was 5/1 for Ranibizumab-PRN, 9/6 for Ranibizumab-T&E, and 7/5 for Aflibercept-Fixed. Both Ranibizumab-T&E and Aflibercept-Fixed also shared the same reduction of median CRT (115 µm), higher than Ranibizumab-PRN (83 µm).ConclusionWe report VA improvement from all three different treatment regimens with both Aflibercept-Fixed and Ranibizumab-T&E regimens achieving the same higher final VA. Aflibercept-Fixed dosing may have more favorable efficacy with the highest VA gain and comparatively lower dosing frequency whereas Ranibizumab-T&E may be more efficient than Ranibizumab-PRN regimen, according to our study.

Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy.

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

Statistical Modelling of the Visual Impact of Subretinal Fluid and Associated Features.

IntroductionThe aim of this study was to develop a statistical model to determine the visual significance of subretinal fluid (SRF) in combination with other constructed optical coherence tomography (OCT) features in patients with wet age-related macular degeneration.MethodsThe project used labelled data from 1211 OCTs of patients with neovascular macular degeneration (nAMD) attending the macular treatment centre of Manchester Royal Eye Hospital to build a statistical model to determine vision for any virtual, constructed OCT. A four-dimensional plot was created to represent the visual impact of SRF in OCTs in the context of the associated OCT characteristics of atrophy and subretinal hyperreflective material (SHRM).ResultsThe plot illustrates that at levels of SRF below 150 µm, the impact of SRF on vision is very low. Increasing the amount of fluid to 200 µm and beyond increases the impact on vision, but only if there is little atrophy or SHRM.ConclusionsThis study suggests that levels of SRF up to around 150 µm thickness on OCT have minimal impact on vision. Greater levels of SRF have greater impact on vision, unless associated with significant amounts of atrophy or SHRM, when the additional effect of the SRF on vision remains low.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-020-00327-w.

Gene Therapy for Neovascular Macular Degeneration, Diabetic Retinopathy, and Diabetic Macular Edema.

J.S.H.: Consultant (4DMT, Adverum, Aerie, Aerpio, Aldeyra, Allegro, Alzheon, Annexon, Apellis, Aprea, Asclepix, Aviceda, Beaver-Visitec, Bionic Vision Technologies, DTx, Eloxx, Galimedix, Genentech, Greybug, Gyroscope, Horizon Therapeutics, iRenix, Iveric, jCyte, Kanghong, LensGen, NGM,Notal Vision, Novartis, Ocular therapeutics, OcuTerra, Oxurion, Palatin, Regeneron, Regenxbio, Stealth, Thea, Verseon, Vinci, Voyant); Research Grants (Aerpio, Aldeyra, Apellis, asclepix, Bayer, Genentech, Graybug, Gyroscope, Hemera, Iveric, Janssen R&D, jCyte, Kanghong, Kodiak, Novartis, Regeneron, Regenxbio, Stealth). P.L.M. declares that there is no conflicts of interest to disclose.

Deliberations of an International Panel of Experts on OCT Angiography Nomenclature of Neovascular Age-Related Macular Degeneration

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).1-4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment.1-6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms "optical coherence tomography angiography" or "OCT angiography" or "OCT-A", AND "neovascular macular degeneration" or "neovascular age-related macular degeneration" or "neovascular AMD" or "nAMD" or "wet age-related macular degeneration" or "wet AMD" or "wet ARMD". A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.