Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options.

Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.

Comparison of Polypoidal Choroidal Vasculopathy Lesion Sizes Measured on Multicolor Imaging and Indocyanine Green Angiography.

Purpose: To evaluate the areas of lesion components of polypoidal choroidal vasculopathy (PCV) measured using multicolor imaging compared to indocyanine green angiography (ICGA). Methods: In a prospective study of 50 consecutive treatment-naïve PCV patients, multicolor imaging and ICGA were performed. The images were independently graded by reading center-certified retinal specialists to confirm the diagnosis of PCV and identify lesion components. The areas of the respective lesion components were compared. Results: The mean age of the participants was 67.8 years. PCV was diagnosed in 96% of eyes using multicolor imaging. The mean numbers of polypoidal lesions identified using ICGA and multicolor were 4.0 and 2.1, respectively (P < 0.001), with mean total polypoidal lesion areas of 0.32 mm2 versus 0.30 mm2 (P = 0.727). The area of the branching vascular network (BVN) on ICGA was 7.8 mm2 compared to 5.7 mm2 on multicolor imaging (P = 0.289). Patients with four or more polypoidal lesions on ICGA had larger differences in total lesion area between ICGA and multicolor imaging (4.07 vs. -0.70 mm2, p = 0.039). Those with total lesion area ≥ 2.0 mm2 on ICGA had larger differences in mean polypoidal lesion number compared to those with smaller areas (2.2 vs. 0.5; P = 0.026). Conclusions: Multicolor imaging is a useful, noninvasive adjunct for detecting PCV lesion components, revealing lesion areas similar to but generally smaller than those seen on ICGA. This is important to consider when making treatment decisions with different imaging modalities. Translational Relevance: New features seen on multicolor imaging can aid in the diagnosis and treatment of PCV.

Multicolor Fundus Imaging of Polypoidal Choroidal Vasculopathy.

PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a variant of neovascular age-related macular degeneration with distinct phenotypes, treatment, and visual prognosis. Multicolor imaging is a novel noninvasive imaging method that enables visualization of structures located at different layers of the retina and may be useful in detecting features of diseases. The features of PCV seen on multicolor imaging have not been studied. We aimed to describe the features of PCV detected using multicolor imaging and to compare these with standard color fundus photography (CFP). DESIGN: Hospital-based, cross-sectional study. PARTICIPANTS: Fifty consecutive treatment-naive patients diagnosed with PCV seen in a tertiary referral center. METHODS: Multimodal imaging was performed using standardized protocols, and included CFP, multicolor imaging, fluorescein angiography, and indocyanine green angiography (ICGA). The CFP and ICGA images were independently graded by reading center-certified retinal specialists to confirm the diagnosis of PCV and identify lesion components. The features of the lesion components seen on multicolor images were compared with those detected using CFP and ICGA. MAIN OUTCOME MEASURES: Frequency and features of lesions associated with PCV, specifically, polyps, branching vascular network (BVN), pigment epithelial detachments (PEDs), hemorrhages, and drusen. RESULTS: The mean age of the 50 participants was 67.9 years, and 60% were male. Polyps were most clearly seen on the infrared reflectance image and detected in 49 of 50 eyes (98%), appearing as dark gray oval lesions with distinct margins. On the multicolor composite images, polyps appeared as dark green oval lesions. The BVN appeared as mottled gray regions on infrared reflectance imaging and were seen less frequently compared with polyps (30/50 eyes, 60%). The margins of the BVN were less distinct compared with polyps. Other clinical features detected using multicolor imaging included PEDs (26%), subretinal hemorrhages (40%), and drusen (66%). CONCLUSIONS: Multicolor imaging is able to detect polypoidal lesions in most patients with PCV. The appearance of PCV lesions on multicolor imaging differs from standard CFP, although the location and shape of lesions correlate well with features seen on CFP and ICGA. Multicolor imaging is a useful, noninvasive adjunct to detect features suggestive of PCV, which may prompt definitive investigations such as ICGA.

Multicolour imaging for the detection of polypoidal choroidal vasculopathy and age-related macular degeneration.

IMPORTANCE: Multicolour is a new imaging technology and its sensitivity for detecting polypoidal choroidal vasculopathy (PCV) and age-related macular degeneration (AMD) has not been well described. BACKGROUND: To evaluate the accuracy of multicolour imaging compared to colour fundus photography (CFP) in differentiating AMD and PCV from normal eyes, and in detecting PCV. DESIGN: Prospective cohort study at a tertiary referral centre. PARTICIPANTS: Fifty consecutive patients with PCV or AMD. METHODS: Standardized multimodal imaging, including CFP, multicolour imaging, and fluorescein and indocyanine green angiography, were graded by a Central Reading Center using standardized grading protocols. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Of 100 eyes, 44 had PCV, 33 had AMD, and 23 were normal. Multicolour imaging had higher specificity (73.9% vs 52.2%) and NPV (94% vs 85.7%) compared to CFP for detecting all types of AMD. For the detection of PCV, multicolour had higher sensitivity (86.4% vs 59.1%) and NPV (89.3% vs 74.3%). Polypoidal lesions were detected in 39 of 44 eyes (88.6%) using multicolour imaging, while the branching vascular network (BVN) was detected in 16 of 44 eyes (36.4%). Using BVN as a parameter, infrared imaging specificity and PPV for detecting PCV were 96.6% and 88.9%, respectively. CONCLUSIONS AND RELEVANCE: Multicolour imaging is superior to standard CFP in differentiating AMD and PCV from normal eyes, and in detecting features of PCV. Specific features seen on multicolour imaging can alert ophthalmologists to the likely presence of these diseases so that additional definitive investigations can be performed.