Treatment Of Age-related Macular Degeneration Research Articles

New ophthalmic drug delivery systems

For decades, topical ophthalmic drug administration through the use of eye drops has been the most widely used technique for the treatment of eye diseases. The development of galenic formulation has led to the use and commercialization of new formulations, such as suspensions, emulsions, and ophthalmic ointments that increase residence time in the site of action. Recently, new administration systems have been developed, such as devices and inserts that provide the sustained release of active substance. Some of these systems are already available on the market, whereas others are still undergoing clinical trials, such as promising systems based on nanostructures (nanocapsules, cyclodextrins, nanoemulsions, etc.). Similarly, various formulations and devices have been developed in the field of intravitreal administration, with different implants available on the European market for the treatment of age-related macular degeneration (AMD), diabetic macular edema, or infections that affect the posterior segment. This review includes current developments in ophthalmic topical and intravitreal drug administration routes as well as those under investigation.

Anti-Vascular Endothelial Growth Factor Drugs for Age-Related Macular Degeneration

What Is the Issue?
 
 Wet age-related macular degeneration (AMD) is a serious health concern that causes reduced vision-related function, poor overall quality of life, and increased health care resource usage.
 Anti-vascular endothelial growth factor (VEGF) drugs are the first-line treatment for wet AMD, and they are injected into the eye. These drugs can slow disease progression but are expensive and require trained medical professionals to administer and monitor treatment response.
 The criteria for initial injection, maintenance, and discontinuation of anti-VEGF drugs in patients with wet AMD remain unclear.
 
 What Did We Do?
 
 To inform decisions about the appropriate use of anti-VEGF drugs to treat adults with wet AMD, CADTH sought to identify and summarize recommendations about criteria for the diagnosis of wet AMD and best practices for subsequent treatment with anti-VEGF drugs.
 An information specialist searched the peer-reviewed and grey literature for clinical practice guidelines published since 2018.
 
 What Did We Find?
 
 Three evidence-based guidelines recommend optical coherence tomography (OCT) to assess patients with suspected wet AMD. The National Institute for Health and Care Excellence (NICE) guidelines then strongly recommend fundus fluorescein angiography only when OCT does not exclude neovascular disease.
 The evidence-based guidelines recommend anti-VEGF drugs for wet or neovascular AMD in adults, particularly for patients with recent disease progression. One guideline suggests starting anti-VEGF treatment as soon as possible once the diagnosis of wet AMD is made.
 The NICE guideline suggests that there may not be any clinically significant distinctions in the effectiveness and safety of various anti-VEGF treatments, including aflibercept, bevacizumab, and ranibizumab, indicating a need for an individualized approach when selecting specific anti-VEGF drugs. However, 1 guideline is inconsistent with NICE, as it suggests choosing bevacizumab first.
 During the maintenance phase of using anti-VEGF drugs, it is important to closely monitor the patient's response and the disease activity and adjust the injection intervals accordingly.
 Guidelines recommend taking an individualized approach and emphasizing active patient involvement in switching and discontinuing anti-VEGF drugs for adults with wet AMD.
 Guidelines or guidance documents without a literature search or unclear methods provided generally consistent recommendations with the included evidence-based guidelines.
 We did not identify any evidence-based guidelines regarding the use of faricimab or brolucizumab. However, NICE published technology appraisals supporting the use of recently approved anti-VEGF drugs (faricimab and brolucizumab) as alternative options for patients who meet similar criteria for treatment with bevacizumab or aflibercept, and under agreed pricing conditions.
 
 What Does It Mean?
 
 All identified guidelines consistently recommend anti-VEGF drugs for adults with wet active AMD, with some providing guidance on the use of OCT and other ophthalmological assessments to identify criteria for starting and adjusting treatment.
 These guidelines recommend personalized and patient-centred approaches for selecting, switching, and discontinuing anti-VEGF medications. Cost is also a crucial factor in decision-making, especially for aflibercept, ranibizumab, and recently approved anti-VEGF drugs such as faricimab and brolucizumab.
 Further research and evidence-based guidelines are necessary to confirm whether newer drugs can be used in similar situations as older drugs.

AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vascular diseases with high prevalence, ranking among the leading causes of blindness and vision loss worldwide. Despite being effective, current treatments for AMD and DR are burdensome for patients and clinicians, resulting in suboptimal compliance and real risk of vision loss. Thus, there is an unmet need for long-lasting alternatives with improved safety and efficacy. Adeno-associated virus (AAV) is the leading vector for ocular gene delivery, given its ability to enable long-term expression while eliciting relatively mild immune responses. Progress has been made in AAV-based gene therapies for not only inherited retinal diseases but also acquired conditions with preclinical and clinical studies of AMD and DR showing promising results. These studies have explored several pathways involved in the disease pathogenesis, as well as different strategies to optimise gene delivery. These include engineered capsids with enhanced tropism to particular cell types, and expression cassettes incorporating elements for a targeted and controlled expression. Multiple-acting constructs have also been investigated, in addition to gene silencing and editing. Here, we provide an overview of strategies employing AAV-mediated gene delivery to treat AMD and DR. We discuss preclinical efficacy studies and present the latest data from clinical trials for both diseases.

Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up).

To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space). This retrospective study included 58 eyes from 53 patients with naïve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections. Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210 ± 45µm vs 191 ± 52µm, p = 0.01) before treatment and (170 ± 47µm vs 179 ± 48µm, p = 0.24) after 60months. BCVA (log MAR) in group 1 vs group 2 was (0.57 ± 0.18 vs 0.53 ± 0.22, p = 0.47) before treatment and (0.59 ± 0.23 vs 0.69 ± 0.16, p = 0.04) after 60months. CMT in group 1 vs group 2 was (398 ± 154µm vs 382 ± 103µm, p = 0.86) before treatment and (297 ± 68µm vs 283 ± 67µm, p = 0.14) after 60months. The number of injections per eye over a period of 60months was significantly higher in group 1 (34.9 ± 11 vs 29.0 ± 14, p = 0.04). The proportion of eyes with subfoveal GA after 60months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p = 0.03). Over the full 60months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.

Understanding barriers and enablers to participation in a proposed online lifestyle intervention for older adults with age-related macular degeneration to guide programme implementation.

Age-related macular degeneration (AMD) is a blinding condition associated with depression, loneliness and unhealthy lifestyle behaviours which drives AMD progression. We have proposed the first online lifestyle intervention for AMD, called Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) to promote positive lifestyle changes and reduce loneliness. This qualitative grounded-theory study explored enablers and barriers to future participation in MINGLE for older adults with AMD. Thirty-one participants were interviewed and thematic analysis revealed nine themes. Enablers to participation were: socialising and learning about AMD, motivation to improve health, programme accessibility and structure. Barriers were: lack of time, technology, limited knowledge regarding holistic interventions, vision-related issues, mobility and negative perception of group interactions. These factors must be considered when developing lifestyle interventions for AMD patients to maximise participation. Supporting technology use and raising awareness about benefits of healthy lifestyle behaviours for AMD may help overcome these barriers.

Analyzing Treatment Patterns for Neovascular Age-related Macular Degeneration with Expansion of the Korean Health Insurance Policy

Purpose: We analyzed the incidence and prevalence of neovascular age-related macular degeneration (AMD) and the treatment patterns of AMD in response to changes in health insurance policies in South Korea.Methods: We retrospectively analyzed the incidence and prevalence of neovascular AMD in patients diagnosed between 2010 and 2019. Data were extracted from the Korean National Health Insurance System database. The incidence and prevalence per 10,000 person-years and corresponding 95% confidence intervals were calculated. Furthermore, we recorded the usage of ranibizumab and aflibercept among newly diagnosed patients with neovascular AMD between 2010 and 2014.Results: In total, 90,012 patients were diagnosed with neovascular AMD between 2010 and 2019. The incidence of neovascular AMD increased with age, except for individuals aged ≥ 90 years. The prevalence of neovascular AMD increased significantly from 30.29 per 10,000 person-years in 2010 to 50.8 per 10,000 person-years in 2019. The rate of intravitreal ranibizumab injections decreased following the introduction of aflibercept in 2014. Patients who switched from ranibizumab to aflibercept exhibited a higher drug switch rate than those who switched from aflibercept to ranibizumab (28.83% vs. 8.40%). Among newly diagnosed patients, approximately 65% received treatment covered by the health insurance system. On average, six injections were administered per year between 2010 and 2019; the number of injections increased in accordance with the maximum limit supported by the government.Conclusions: The incidence and prevalence of neovascular AMD demonstrated an increasing trend. The treatment patterns are influenced by changes in government funding support policies. These findings provide valuable information for planning neovascular AMD treatment.

Vitreous body in the treatment of exudative age-related macular degeneration : The medium is the message

Intravitreal anti-vascular endothelial growth factor (VEGF) is the standard treatment for exudative age-related macular degeneration (AMD). The constitution of the vitreomacular interface varies greatly in cases of attached (with or without traction) or detached vitreous body, which can impact the effectiveness of the anti-VEGF treatment. Based on the current literature this article displays the current state of the science on whether the constitution of the vitreous body has an effect on the anti-VEGF treatment. The published data extracted from current trials and post hoc analyses concerning this topic are presented and put into the clinical context. The presence of a vitreomacular adhesion reduces the efficacy of anti-VEGF treatment of exudative AMD. Posterior vitreous body detachment represents apositive prognostic factor concerning the efficacy of anti-VEGF treatment but not necessarily the prognosis for visual acuity. Patients with attached vitreous body need a more intensive treatment monitoring compared to patients with detached vitreous body. Therefore, in eyes with initial posterior vitreous body detachment receiving atreat and extend regimen, the interval between anti-VEGF injections can be extended to 4instead of 2weeks without endangering the success of treatment.

End binding-3 inhibitor activates regenerative program in age-related macular degeneration

Wet age-related macular degeneration (AMD), characterized by leaky neovessels emanating from the choroid, is a main cause of blindness. As current treatments for wet AMD require regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) biologics, there is a need for the development of less invasive treatments. Here, we designed an allosteric inhibitor of end binding-3 (EB3) protein, termed EBIN, which reduces the effects of environmental stresses on endothelial cells by limiting pathological calcium signaling. Delivery of EBIN via eye drops in mouse and non-human primate (NHP) models of wet AMD prevents both neovascular leakage and choroidal neovascularization. EBIN reverses the epigenetic changes induced by environmental stresses, allowing an activation of a regenerative program within metabolic-active endothelial cells comprising choroidal neovascularization (CNV) lesions. These results suggest the therapeutic potential of EBIN in preventing the degenerative processes underlying wet AMD.

Treatment Methods Dry Form of Age Macular Degeneration — History and Prospects. Review

Age related macular degeneration is a leading cause of vision loss and an increasing problem of disability throughout the world among adults. That revue covers historical points, risk factors, pathogenesis, classification and current treatment ways of that pathology. The causes of age-related macular degeneration are not fully understood, in spite of keeping a great amount of knowledge at etiology, pathogenesis, diagnosis and modern types of treatment. The problem of age-related macular degeneration treatment has remained actual nowadays. Now, the medicine doesn’t have etiotropic treatment of AMD, because we still don’t know a definite etiologic factor of this developing disease. The main treatment for wet AMD is the injection of medications called anti-VEGF agents. Currently, treatment of dry age-related macular degeneration includes modification of risk factors (stop smoking, healthy life style and etc) and dietary supplements containing a combination of certain ingredients (vitamin C, vitamin E, zinc, copper, and lutein with zeaxanthin or beta-carotene) may be able to slow the progression of the disease. The disadvantage of current treatment methods is a narrow focus at one of the pathogenesis components or using as symptomatic therapy. The analysis of literature date has allowed noticing of using of an extracorporeal hemocorrection as perspective way at exploration of new methods of treatment of dry age-related macular degeneration.

Shedding Light on Photobiomodulation Therapy for Age-Related Macular Degeneration: A Narrative Review.

Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD. A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review. The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patientswith AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials. Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.

Choriocapillaris Impairment Is Associated With Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration.

Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD. One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging. In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001). Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.

The Safety of Anti-VEGF Treatment, in the Context of the Retinal Nerve Fibre Layer, in Patients with Wet Age-Related Macular Degeneration: A Review.

Anti-vascular endothelial growth factor (VEGF) drugs are widely used in modern ophthalmology, especially in treating macular disorders like age-related macular degeneration or diabetic macular edema. Protocols for such treatments include repeated administration of intravitreal injections, with the volume of drug injected into the vitreous chamber seemingly high enough to cause an increase in intraocular pressure. Hence, questions might arise if such therapeutic approaches are safe for ocular tissue. Moreover, anti-VEGF compounds may theoretically harm the retinal nerve fibers due to the inhibition of VEGF and its neuroprotective effects. Thus, this manuscript aims to review the literature regarding studies evaluating the retinal nerve fiber layer (RNFL) in eyes receiving anti-VEGF treatment due to age-related macular degeneration. The RNFL was chosen as a subject of this review, as it is the innermost retinal layer exposed to the direct action of intravitreally administered drugs. The results of the available studies remain inconclusive. Most researchers seem to confirm the safety of the anti-VEGF treatment in wet age-related macular degeneration, at least regarding the retinal nerve fiber layer. However, some authors noticed that the influence of anti-VEGFs on RNFL could become apparent after more than thirty injections. Nonetheless, the authors of all studies agree that further, long-term observations are needed to help clinicians understand the effect of anti-VEGF treatment on the dynamics of changes in the thickness of retinal nerve fibers in patients with the wet form of age-related macular degeneration.

Treatment of dry age-related macular degeneration: A review.

Age-related macular degeneration is a global disease with a significant societal impact. The advent of anti-vascular endothelial growth factor therapy (anti-VEGF) has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). Dry age-related macular degeneration (dAMD) is being investigated for possible therapeutic options. The therapeutic categories undergoing clinical trials include complement pathway inhibitors, visual cycle modulators, reduction of toxic byproducts, antioxidative therapy, neuroprotective agents, laser therapy, surgical options, gene therapy, stem cell therapy, and miscellaneous treatments. Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have recently shown phase 3 clinical trial evidence of a reduction in the growth of geographic atrophy. In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA).

Vitreoretinal surgery in age-related macular degeneration

The structure of the vitreous body, its interaction with the retinal surface and tractive alterations of the vitreoretinal interface may play arole in the pathogenesis and the development of age-related macular degeneration (AMD). From clinical trials it can be concluded that posterior vitreous detachment (PVD) or vitreous removal may protect against the development of neovascular AMD. Vitreomacular adhesions may promote neovascular AMD and may have an impact on the efficacy and frequency of intravitreal vascular endothelial growth factor (VEGF) inhibition. Therefore, vitreomacular surgery may be considered as atreatment option in selected cases. Peeling of epimacular membranes and the internal limiting membrane (ILM) may contribute to stabilizing visual acuity and reducing the treatment burden of current intravitreal pharmacotherapy. At present, surgical interventions in AMD are mainly performed in cases of submacular hemorrhage involving the fovea. The treatment is not standardized and consists of liquefaction of the blood using recombinant tissue plasminogen activator (rTPA) and its pneumatic displacement, potentially combined with VEGF inhibition. Other submacular surgical strategies, such as choroidal neovascularization (CNV) extraction, macular translocation or transplantation of retinal pigment epithelium (RPE) are currently limited to selected cases as asalvage treatment; however, the development of these submacular surgical interventions has formed the basis for new approaches in the treatment of dry and neovascular AMD including submacular or intravitreal gene and stem cell therapy.

Traditional Chinese medicine for age-related macular degeneration: A clinical evidence map between 2000 and 2022

Abstract Background We systematically searched and summarized clinical studies on traditional Chinese medicine (TCM) for age-related macular degeneration (AMD) with the method of evidence map. We aimed to provide evidence and research direction for the prevention or treatment of AMD with TCM in the future. Materials and methods We searched PubMed, Web of Science, EMBASE, and Chinese databases including CNKI (Chinese National Knowledge Infrastructure), WanFang and VIP, Clinical Trials.gov, and Chinese Clinical Trial Registry Center studies on the prevention or treatment of TCM for AMD from January 2000 to November 2022. We showed distribution features of these studies in the form of text description, graphs, and tables. Results The final 258 articles included 245 clinical studies, 9 systematic reviews or meta-analyses, and 4 guidelines, expert consensus, or clinical pathway. After analyzing the articles with a focus on the stage of AMD, study type, sample size, intervention measures, outcome indicators, and the quality of evidence, we found that the studies were increasing, most of which were wet AMD, the main study type was randomized controlled trials, and the sample size was mostly fewer than 100 cases. Different interventions of TCM, such as Chinese medicine, Chinese patent medicine, or acupuncture, showed the potential benefits of improving vision, reducing fundus lesions, and alleviating some uncomfortable symptoms. However, the sample size of these studies was small. The outcome indicators were not unified, and the stage of AMD was unclear. The quality of articles was lower, and there were few studies on early AMD. The advantages of TCM for the prevention or treatment of AMD remained unclear. Conclusions Early intervention will be the focus and direction of AMD in the prevention or treatment of TCM, and more standardized clinical studies of TCM for early AMD need to be designed and carried out in the future.

Causal Effects of Gut Microbiota on Age-Related Macular Degeneration: A Mendelian Randomization Study.

Recently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut-retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD. The study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 × 10-8). Additionally, a separate group of SNPs below the locus-wide significance level (1 × 10-5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants. IVW results showed that genus Anaerotruncus (P=5.00 × 10-3), genus Candidatus Soleaferrea (P=1.83 × 10-2), and genus unknown id.2071 (P=3.12 × 10-2) were protective factors for AMD. The Eubacterium oxidoreducens group (P=3.17 × 10-2), genus Faecalibacterium (P=2.67 × 10-2), and genus Ruminococcaceae UCG-011 (P=4.04 × 10-2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P>0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P>0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD. We confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.

Response of Pigment Epithelial Detachment to Three-Loading-Dose of Intravitreal Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration

Objective: Response of pigment epithelial detachment (PED) to three loading dose of intravitreal bevacizumab (IVB) treatment in neovascular age-related macular degeneration (nAMD) cases.&#x0D; Methods: OCT findings (PED height (µm), diameter(µm) and area (mm²), central macular thickness (CMT), central choroidal thickness (CCT), intraretinal fluid (IRF), subretinal fluid (SRF)), and morphological features of macular neovascularization (MNV) in OCTA before and after three loading doses of IVB were examined and compared.&#x0D; Results: Forty-two eyes of 42 naive nAMD patients with PED were included. Fifteen patients had serous and 27 patients had fibrovascular PED. After three loading doses, best corrected visual acuity (BCVA) (in Snellen) increased from 0.22±0.19 to 0.29±0.22 (p

Medicare Part B Spending on Macular Degeneration Treatments Associated With Manufacturer Payments to Ophthalmologists

Age-related macular degeneration (ARMD) therapies aflibercept and ranibizumab are among the highest-cost Medicare Part B drugs, even though off-label use of lower-cost bevacizumab is clinically noninferior. Payments from manufacturers of these ARMD therapies to ophthalmologists are hypothesized to be factors in ophthalmologists' therapeutic choice, controlling for ophthalmologist and patient characteristics. To assess the association between manufacturer payments to ophthalmologists and choice of ARMD treatment as well as to identify ophthalmologist-level characteristics associated with prescribing lower-cost ARMD therapies. This retrospective cross-sectional study of longitudinal (2013-2019) Medicare Part B data was conducted from December 2021 to December 2022. Ophthalmologists prescribing aflibercept (manufactured by Regeneron Pharmaceuticals Inc), rabinizumab, or bevacizumab (both manufactured by Genentech Inc) for ARMD treatment of Medicare Part B beneficiaries were included. Data on manufacturer payments to ophthalmologists were obtained from the Open Payments database. The primary outcome was the percentage of bevacizumab prescribed by ophthalmologists among all ARMD therapies. Regression analysis assessed variation in bevacizumab prescribing by acceptance of manufacturer payments as well as by ophthalmologist and patient characteristics. Ophthalmologist characteristics were duration of practice and Medicare Administrative Contractor region, and patient characteristics were aggregated at the ophthalmologist level and included mean beneficiary age, percentage of dual-eligible beneficiaries, mean beneficiary risk score, and percentage of White beneficiaries. Savings were estimated by projecting the change in bevacizumab use had ophthalmologists not accepted manufacturer payments, controlling for all ophthalmologist and patient characteristics and comparing with observed use and costs. A total of 21 584 ophthalmologists (18 489 males [85.7%]) were included. Ophthalmologists who accepted manufacturer payments were significantly less likely to prescribe bevacizumab (28.0% [95% CI, 24.6%-42.5%] of patients) compared with those who did not accept manufacturer payments (45.8% [95% CI, 44.5%-47.1%]). Ophthalmologists who saw dual-eligible beneficiaries had greater bevacizumab prescribing (50.0% [95% CI, 40.6%-68.3%] in the highest quartile vs 36.1% [95% CI, 33.5%-38.8%] in the lowest quartile; β coefficient, 0.139; P < .001), while those who saw patients with higher mean beneficiary risk scores had lower bevacizumab use (38.0% [95% CI, 23.7%-44.1%] in the highest quartile vs 48.2% [95% CI, 45.5%-50.8%] in the lowest quartile; β coefficient, -0.102, P < .001). Had ophthalmologists who accepted manufacturer payments prescribed ARMD drugs as those who did not accept payments, Medicare spending on these treatments would have been $642 779 703.08 lower from 2013 to 2019, a 2.0% savings. Results of this cross-sectional study suggest that drug manufacturer payments to ophthalmologists were associated with selection of higher-cost therapies for ARMD, which is a factor in increased Medicare and patient spending. Development of manufacturer payment models that encourage ophthalmologists to choose lower-cost therapies are needed.

Faricimab: Transforming the Future of Macular Diseases Treatment - A Comprehensive Review of Clinical Studies.

Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab's application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.

Efficacy, Safety, and Durability of Brolucizumab: An 8-Month Post-Marketing Surveillance Analysis.

Brolucizumab (Beovu®) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns. We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world. This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020. Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events. The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001). Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER.