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14 pages, 2067 KiB

Open AccessArticle

Factors Affecting Visual Acuity After Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration: A Multicenter Study in Japan

by Aoi Kominami, Shuhei Tomita, Aki Kato, Koichi Ono, Masaru Takeuchi, Masaya Imazeki, Hiroto Terasaki, Yuki Yamamoto, Tatsuya Jujo, Makiko Wakuta, Hisashi Matsubara, Yoshinori Mitamura, Mineo Kondo, Kazuhiro Kimura, Hitoshi Takagi, Fumi Gomi, Taiji Sakamoto and Tsutomu Yasukawa

J. Clin. Med. 2024, 13(20), 6244; https://doi.org/10.3390/jcm13206244 - 19 Oct 2024

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Abstract

Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the [...] Read more.

Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the visual prognosis in clinical settings. This study aimed to identify the factors that affect the visual prognosis in patients with nvAMD treated with anti-VEGF therapy. Methods: We conducted a multicenter retrospective cohort study at eight tertiary referral centers in Japan, where we reviewed the medical records of patients newly diagnosed with nvAMD between January 2014 and December 2019. These patients had started treatment with either ranibizumab (0.5 mg) or aflibercept (2.0 mg) and were followed for at least 1 year. We evaluated the impact of the disease type, systemic factors, and initial fundus findings on the best-corrected visual acuity (BCVA) at 1 year. Results: This study included 182 patients (129 men, 53 women), with a mean age of 75.0 ± 8.6 years. The disease types were categorized as typical AMD (53%), polypoidal choroidal vasculopathy (PCV) (43%), and retinal angiomatous proliferation (RAP) (4%). Univariate analysis identified age, the baseline logarithm of the minimum angle of resolution BCVA, intraretinal fluid (IRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM). Multivariate analysis identified the following significant risk factors associated with vision worsening: age, smoking history, diabetes, and the presence of IRF and PED. Conclusions: The presence of IRF, PED, and SHRM at the start of treatment and a history of smoking and diabetes may be associated with a poor visual prognosis in patients with nvAMD. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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13 pages, 10438 KiB

Open AccessArticle

Clinical Characteristics of Punctate Hyperfluorescence Spots in the Fellow Eye of Patients with Unilateral Macular Neovascularization with No Drusen

by Hiroyuki Kamao, Katsutoshi Goto, Yuto Date, Ryutaro Hiraki, Kenichi Mizukawa and Atsushi Miki

J. Clin. Med. 2024, 13(18), 5394; https://doi.org/10.3390/jcm13185394 - 12 Sep 2024

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Abstract

Objectives: To assess the clinical characteristics of patients with macular neovascularization (MNV) with no drusen in the fellow eye, we investigated the incidence of MNV in fellow eyes and the outcomes of intravitreal aflibercept (IVA) monotherapy in MNV eyes of patients with [...] Read more.

Objectives: To assess the clinical characteristics of patients with macular neovascularization (MNV) with no drusen in the fellow eye, we investigated the incidence of MNV in fellow eyes and the outcomes of intravitreal aflibercept (IVA) monotherapy in MNV eyes of patients with unilateral MNV with a punctate hyperfluorescence spot (PHS) in the fellow eye. Methods: We retrospectively studied 58 treatment-naïve patients with unilateral MNV with no drusen in the fellow eye. Patients were classified into a PHS group (n = 29) or no-PHS group (n = 29) based on the presence of PHS. We evaluated the incidence of MNV in the fellow eye, and the retreatment rate after initiation of three monthly aflibercept injections over one year. Results: Fellow eyes in the PHS group had a thicker choroid (p < 0.05) and higher prevalence of pachychoroid pigment epitheliopathy (PPE) (p < 0.001). MNV eyes in the PHS group had a thicker choroid (p = 0.09). The PHS group had a lower retreatment rate (p < 0.05) and required fewer injections (p < 0.05) than the no-PHS group. MNV developed in one eye in both the PHS and no-PHS groups, and both cases occurred in areas of hypofluorescence on indocyanine green angiography within the PPE area before the onset of MNV. Conclusions: The PHS group frequently exhibited pachychoroid disease characteristics and responded better to IVA monotherapy than the no-PHS group. These groups may represent distinct populations of patients with unilateral MNV with no drusen in the fellow eye. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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11 pages, 945 KiB

Open AccessArticle

Pathogenesis of Pachyvein Formation in Central Serous Chorioretinopathy: A Hydrodynamic Analysis

by Okihiro Nishi, Yutaro Nishi, Miki Tatsumichi and Tsutomu Yasukawa

J. Clin. Med. 2024, 13(16), 4777; https://doi.org/10.3390/jcm13164777 - 14 Aug 2024

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Abstract

Objectives: To attain an understanding of pachyvein formation seen with central serous chorioretinopathy (CSC) by measuring the choroidal blood flow (CBF) velocity and to apply the findings to existing hydrodynamic theorems. Methods: Nineteen subjects with monocular CSC (mean age 51.8 ± 12.7 years) [...] Read more.

Objectives: To attain an understanding of pachyvein formation seen with central serous chorioretinopathy (CSC) by measuring the choroidal blood flow (CBF) velocity and to apply the findings to existing hydrodynamic theorems. Methods: Nineteen subjects with monocular CSC (mean age 51.8 ± 12.7 years) were included. Laser speckle flowgraphy measured the mean blur rate (MBR) in the foveal and perifoveal regions, and the findings were applied to the Equation of Continuity (Q = AV) and Bernoulli’s theorem (1/2V² + P/ρ = constant). Results: The mean foveal/perifoveal MBRs in the CSC eyes were 6.4 ± 3.2/9.6 ± 3.2 (p < 0.001). The mean MBRs in the non-CSC eyes were 8.3 ± 3.2/7.9 ± 2.4 (p = 0.37). The significant foveal CBF velocity decrease in CSC eyes occurs because of exudation from the hyperpermeable choriocapillaris. The subsequent decrease in blood volume due to the exudation elicits a decrease in the blood flow velocity in the inferior venules in accordance with the Equation of Continuity. The decrease in the blood flow velocity may result in an elevated blood flow pressure in the inferior venules and veins at the exudation site, in accordance with Bernoulli’s theorem. Conclusion: A significant decrease in the foveal MBR may result from exudation from the hyperpermeable macular choriocapillaris. This decreased velocity may elicit a blood pressure elevation that can expand the inferior venules and veins at the exudation site, so-called pachyvein and pachychoroid formation. The application of hydrodynamic theorems to the measurement of ocular blood flow can provide new insights into the understanding of the pathogenesis of chorioretinal disease. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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8 pages, 721 KiB

Open AccessArticle

Recurrence Rate during 5-Year Period after Suspension of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration

by Shinichiro Chujo, Hisashi Matsubara, Yoko Mase, Kumiko Kato and Mineo Kondo

J. Clin. Med. 2024, 13(15), 4317; https://doi.org/10.3390/jcm13154317 - 24 Jul 2024

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Abstract

Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF [...] Read more.

Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF drugs were studied. All met the treatment suspension criteria and were followed for 5 years after the suspension of the anti-VEGF treatment. Patients with a recurrence within one year were placed in Group A, and patients with a recurrence between 1 and 5 years were placed in Group B. The rate and time of a recurrence were analyzed using the Kaplan–Meier method. We also examined whether there were differences in the baseline factors of age, sex, subtype, treatment period, and treatment interval between Groups A and B. Results: Twenty-five of 34 eyes (73.5%) had a recurrence within 5 years of stopping the anti-VEGF treatments. Thirteen (52.0%) of the 25 eyes had a recurrence within 1 year, 4 (16.0%) eyes between 1 and 2 years, 4 (16.0%) eyes between 2 and 3 years, 2 (8%) between 3 and 4 years, and 2 eyes (8%) between 4 and 5 years. The baseline factors were not significantly different between Groups A and B. Conclusions: The results showed that the recurrence rate was highest within one year after the suspension of the anti-VEGF treatments, with a number of recurrences one year after the suspension. Clinicians should remember that nAMD may recur several years after the suspension of anti-VEGF treatments. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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12 pages, 1665 KiB

Open AccessArticle

Clinical Characteristics of Unilateral Macular Neovascularization Patients with Pachydrusen in the Fellow Eye

by Hiroyuki Kamao, Erika Mitsui, Yuto Date, Katsutoshi Goto, Kenichi Mizukawa and Atsushi Miki

J. Clin. Med. 2024, 13(13), 3757; https://doi.org/10.3390/jcm13133757 - 27 Jun 2024

Cited by 1 | Viewed by 753

Abstract

Background/Objectives: To approach the clinical properties of pachydrusen that differ from conventional drusen, we investigated the incidence of macular neovascularization (MNV) in fellow eyes and the treatment outcomes of intravitreal aflibercept (IVA) in MNV eyes of unilateral MNV patients with pachydrusen in [...] Read more.

Background/Objectives: To approach the clinical properties of pachydrusen that differ from conventional drusen, we investigated the incidence of macular neovascularization (MNV) in fellow eyes and the treatment outcomes of intravitreal aflibercept (IVA) in MNV eyes of unilateral MNV patients with pachydrusen in the fellow eye. Methods: We retrospectively studied 261 consecutive patients with treatment-naïve unilateral MNV. Patients were classified into four groups according to the type of drusen in the fellow eye: the pachydrusen group (n = 49), the soft drusen group (n = 63), the subretinal drusenoid deposit (SDD) group (n = 24), and the no drusen group (n = 125). The development of the MNV in the fellow eye was evaluated for five years, and the retreatment proportion after three monthly aflibercept injections was evaluated for one year. Results: The choroidal thickness in the fellow eyes and MNV eyes was the greatest in the pachydrusen group (all p < 0.001). The 5-year incidence of MNV in the pachydrusen group was similar to that in the soft drusen group and no drusen group. The pachydrusen group had a lower retreatment rate than the other groups did (pachydrusen group: 46.4%; soft drusen group: 78.1%; SDDs: 87.5%; no drusen group: 83.3%). Conclusions: Unilateral MNV patients with pachydrusen in the fellow eye had a lower retreatment rate (46.4%/1 year); therefore, aflibercept monotherapy using the PRN regimen is one of the preferred treatment methods for MNV patients with pachydrusen in the fellow eye. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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11 pages, 1356 KiB

Open AccessArticle

Short-Term Real-World Outcomes of Intensive Aflibercept Injection for Refractory Neovascular Age-Related Macular Degeneration

by Wonyung Son and Min Sagong

J. Clin. Med. 2024, 13(12), 3503; https://doi.org/10.3390/jcm13123503 - 15 Jun 2024

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Abstract

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included [...] Read more.

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 μm to 336.38 ± 121.67 μm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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12 pages, 1451 KiB

Open AccessArticle

Switching from a Fixed Monthly Aflibercept Regimen to Bi-Monthly Brolucizumab in Refractory Cases of Neovascular Age-Related Macular Degeneration

by Minhee Kim, Ji Eon Kang and Young Gun Park

J. Clin. Med. 2024, 13(12), 3434; https://doi.org/10.3390/jcm13123434 - 12 Jun 2024

Cited by 1 | Viewed by 851

Abstract

Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from [...] Read more.

Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). Results: The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 μm, respectively; p = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 μm (p < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 μm, which decreased to 233.0 ± 71.2 μm (p = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT (p = 0.012). Conclusions: Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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13 pages, 2992 KiB

Open AccessArticle

Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration

by Michiko Ando, Aki Kato, Masayo Kimura, Shuntaro Ogura, Soichiro Kuwayama, Aoi Kominami, Satoshi Kuwayama, Tomohiro Obayashi, Ryota Ando, Takafumi Monoe, Hiroshi Morita and Tsutomu Yasukawa

J. Clin. Med. 2024, 13(8), 2417; https://doi.org/10.3390/jcm13082417 - 21 Apr 2024

Cited by 1 | Viewed by 1012

Abstract

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in [...] Read more.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm³ to 9.6 mm³, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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12 pages, 14199 KiB

Open AccessFeature PaperArticle

Wide-Field Choroidal Thickness Analysis after Half-Fluence Photodynamic Therapy Combined with Intravitreal Aflibercept Injection in Pachychoroid Neovasculopathy

by Yosuke Fukuda, Shoji Notomi, Satomi Shiose, Yusuke Maehara, Kohei Kiyohara, Sawako Hashimoto, Kumiko Kano, Keijiro Ishikawa, Toshio Hisatomi and Koh-Hei Sonoda

J. Clin. Med. 2024, 13(6), 1608; https://doi.org/10.3390/jcm13061608 - 11 Mar 2024

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Abstract

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection [...] Read more.

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9 and 9–18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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12 pages, 2958 KiB

Open AccessArticle

Evaluation of Choroidal Structure in Type 1 Macular Neovascularization Using Different Optical Coherence Tomography Analyses: Scale Bar and Binarization

by Hiromasa Hirai, Mariko Yamashita, Nobuo Ijuin, Hironobu Jimura, Tomo Nishi, Nahoko Ogata and Tetsuo Ueda

J. Clin. Med. 2024, 13(5), 1383; https://doi.org/10.3390/jcm13051383 - 28 Feb 2024

Cited by 1 | Viewed by 922

Abstract

Background: Macular neovascularization (MNV) has been evaluated by optical coherence tomography (OCT) imaging using various approaches. However, few studies have examined their differences. This study analyzed type 1 MNV with a combination of two approaches: scale bar and binarization. Methods: We enrolled 84 [...] Read more.

Background: Macular neovascularization (MNV) has been evaluated by optical coherence tomography (OCT) imaging using various approaches. However, few studies have examined their differences. This study analyzed type 1 MNV with a combination of two approaches: scale bar and binarization. Methods: We enrolled 84 patients with untreated type 1 MNV. We measured choroidal parameters using a scale bar and defined the ratios of superficial choroidal thickness to choroidal vessel diameter (SV ratios). We also used binarization and calculated the ratios of the luminal to the choroidal area (LC ratios) in two directions (horizontal and vertical). Results: Fifty-one patients (61%) were classified as having polyps. SV ratios in the group with polyps were significantly lower than in the group without (p < 0.001). The receiver operating characteristic (ROC) curve showed that the SV ratio was predictive of polyps (AUC 0.733, 95% CI: 0.621–0.844). In patients without polyps, horizontal LC ratios were significantly higher in a subgroup with subretinal fluid than in those without (p = 0.047). The ROC curve showed that the LC ratio was predictive of subretinal fluid (AUC 0.722, 95% CI: 0.517–0.926). Conclusion: The SV ratio reflects the MNV disease type, whereas the LC ratio reflects MNV disease activity. Establishing cut-off values for each ratio may be useful for MNV diagnosis. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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13 pages, 3022 KiB

Open AccessArticle

Structure-Function Correlation of Retinal Fibrosis in Eyes with Neovascular Age-Related Macular Degeneration

by Markus Schranz, Stefan Sacu, Gregor S. Reiter, Magdalena Baratsits, Silvia Desissaire, Michael Pircher, Georgios Mylonas, Christoph Hitzenberger, Ursula Schmidt-Erfurth and Philipp Ken Roberts

J. Clin. Med. 2024, 13(4), 1074; https://doi.org/10.3390/jcm13041074 - 14 Feb 2024

Cited by 1 | Viewed by 1168

Abstract

Purpose: To assess retinal function in areas of presumed fibrosis due to neovascular age-related macular degeneration (nAMD), using multimodal imaging and structure-function correlation. Design: Cross-sectional observational study. Methods: 30 eyes of 30 consecutive patients with nAMD with a minimum history of one year [...] Read more.

Purpose: To assess retinal function in areas of presumed fibrosis due to neovascular age-related macular degeneration (nAMD), using multimodal imaging and structure-function correlation. Design: Cross-sectional observational study. Methods: 30 eyes of 30 consecutive patients with nAMD with a minimum history of one year of anti-vascular endothelial growth factor therapy were included. Each patient underwent microperimetry (MP), color fundus photography (CFP), standard spectral-domain-based OCT (SD-OCT), and polarization sensitive-OCT (PS-OCT) imaging. PS-OCT technology can depict retinal fibrosis based on its birefringence. CFP, SD-OCT, and PS-OCT were evaluated independently for the presence of fibrosis at the corresponding MP stimuli locations. MP results and morphologic findings in CFP, SD-OCT, and PS-OCT were co-registered and analyzed using mixed linear models. Results: In total, 1350 MP locations were evaluated to assess the functional impact of fibrosis according to a standardized protocol. The estimated means of retinal areas with signs of fibrosis were 12.60 db (95% confidence interval: 10.44–14.76) in CFP, 11.60 db (95% COI: 8.84–14.36) in OCT, and 11.02 db (95% COI 8.10–13.94) in PS-OCT. Areas evaluated as subretinal fibrosis in three (7.2 db) or two (10.1 db) modalities were significantly correlated with a lower retinal sensitivity than a subretinal fibrosis observed in only one (15.3 db) or none (23.3 db) modality (p < 0.001). Conclusions: CFP, SD-OCT and PS-OCT are all suited to detect areas of reduced retinal sensitivity related to fibrosis, however, a multimodal imaging approach provides higher accuracy in the identification of areas with low sensitivity in MP (i.e., impaired retinal function), and thereby improves the detection rate of subretinal fibrosis in nAMD. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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12 pages, 1827 KiB

Open AccessArticle

Two-Year Follow-Up Study of Patients with Neovascular Age-Related Macular Degeneration Undergoing Anti-VEGF Treatment during the COVID-19 Pandemic

by Jae-Gon Kim, Yu Cheol Kim and Kyung Tae Kang

J. Clin. Med. 2024, 13(3), 867; https://doi.org/10.3390/jcm13030867 - 1 Feb 2024

Cited by 1 | Viewed by 1009

Abstract

Background: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. Methods: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This [...] Read more.

Background: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. Methods: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic. Results: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p < 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year. Conclusion: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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16 pages, 3807 KiB

Open AccessArticle

Face Recognition Characteristics in Patients with Age-Related Macular Degeneration Determined Using a Virtual Reality Headset with Eye Tracking

by Nina Žugelj, Lara Peterlin, Urša Muznik, Pia Klobučar, Polona Jaki Mekjavić, Nataša Vidović Valentinčić and Ana Fakin

J. Clin. Med. 2024, 13(2), 636; https://doi.org/10.3390/jcm13020636 - 22 Jan 2024

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Abstract

Background and Objectives: Face recognition is one of the most serious disabilities of patients with age-related macular degeneration (AMD). Our purpose was to study face recognition using a novel method incorporating virtual reality (VR) and eye tracking. Materials and Methods: Eighteen patients with [...] Read more.

Background and Objectives: Face recognition is one of the most serious disabilities of patients with age-related macular degeneration (AMD). Our purpose was to study face recognition using a novel method incorporating virtual reality (VR) and eye tracking. Materials and Methods: Eighteen patients with AMD (seven male; median age 83 years; 89% with bilateral advanced AMD) and nineteen healthy controls (five male; median age 68 years) underwent the face recognition test IC FACES (Synthesius, Ljubljna, Slovenia) on a VR headset with built-in eye tracking sensors. Analysis included recognition accuracy, recognition time and fixation patterns. Additionally, a screening test for dementia and imaging with fundus autofluorescence and optical coherence tomography was performed. Results: AMD patients had significantly lower face recognition accuracy (42% vs. 92%; p < 0.001) and longer recognition time (median 4.0 vs. 2.0 s; p < 0.001) in comparison to controls. Both parameters were significantly worse in patients with lower visual acuity. In both groups, eye-tracking data revealed the two classical characteristics of the face recognition process, i.e., fixations clustering mainly in the nose–eyes–mouth triangle and starting observation in the nasal area. Conclusions: The study demonstrates usability of a VR headset with eye tracking for studying visual perception in real-world situations which could be applicable in the design of clinical studies. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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10 pages, 1856 KiB

Open AccessArticle

Comparison of Loading Dose between Aflibercept and Faricimab for Neovascular Age-Related Macular Degeneration

by Chikako Hara, Masaki Suzue, Satoko Fujimoto, Yoko Fukushima, Kaori Sayanagi, Kentaro Nishida, Kazuichi Maruyama, Shigeru Sato and Kohji Nishida

J. Clin. Med. 2024, 13(2), 385; https://doi.org/10.3390/jcm13020385 - 10 Jan 2024

Cited by 5 | Viewed by 2452

Abstract

Background: Recently, faricimab was approved as the new drug for neovascular age-related macular degeneration (nAMD). We lack the knowledge to choose between the existing drug and this new drug to use for treatment-naïve nAMD cases. In this study, we compared the functional and [...] Read more.

Background: Recently, faricimab was approved as the new drug for neovascular age-related macular degeneration (nAMD). We lack the knowledge to choose between the existing drug and this new drug to use for treatment-naïve nAMD cases. In this study, we compared the functional and morphologic effects in loading dose between patients with treatment-naïve nAMD treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in a clinical setting. Method: This retrospective study included 30 eyes of 28 patients who started treatment with IVA between June and September 2022 and 30 eyes of 29 patients who were administered IVF between October 2022 and March 2023. All patients received three monthly IVA or IVF. The best corrected visual acuity (BCVA), central retinal thickness (CRT), and the proportion of eyes with residual exudative change at baseline and 1,2, and 3 months after initial treatment were compared between the groups. Results: The mean BCVA significantly improved from pre-treatment after the loading dose in the IVA group (0.46 ± 0.46–0.36 ± 0.37, p = 0.0047) but not in the IVF group (0.46 ± 0.41–0.44 ± 0.45, p = 0.60). The mean CRT significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group 2 months after the first treatment (p = 0.026). The analysis of cases that achieved complete resolution of exudative changes after the loading dose showed that the IVA group had a significant improvement in the BCVA, whereas the IVF group did not (p = 0.0047 and 0.20, respectively). Conclusions: Although both IVA and IVF significantly improved CRT, the BCVA improved significantly in the IVA group but not in the IVF group. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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10 pages, 545 KiB

Open AccessArticle

Anatomical and Functional Outcomes with Prompt versus Delayed Initiation of Anti-VEGF in Exudative Age-Related Macular Degeneration

by Assaf Gershoni, Edward Barayev, Rabeea H. Daood, Maureen Yogev, Orly Gal-Or, Olga Reitblat, Maria Tsessler, Michal Schaap Fogler, Raimo Tuuminen and Rita Ehrlich

J. Clin. Med. 2024, 13(1), 111; https://doi.org/10.3390/jcm13010111 - 25 Dec 2023

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Abstract

Purpose: To investigate the correlation between time from diagnosis of treatment-naïve exudative age-related macular degeneration (AMD) to the introduction of anti-VEGF treatment and anatomical and functional outcomes. Design: Retrospective cohort study. Methods: Included were treatment-naïve exudative AMD patients who presented to a single [...] Read more.

Purpose: To investigate the correlation between time from diagnosis of treatment-naïve exudative age-related macular degeneration (AMD) to the introduction of anti-VEGF treatment and anatomical and functional outcomes. Design: Retrospective cohort study. Methods: Included were treatment-naïve exudative AMD patients who presented to a single tertiary medical center between 2012 and 2018. All patients were treated within the first 30 days of their diagnosis with three monthly intravitreal injections of bevacizumab. Patients were divided into three groups: group 1 (prompt anti-VEGF) were injected with bevacizumab within ten days, group 2 (intermediate anti-VEGF) within 11–20 days, and group 3 (delayed anti-VEGF) within 21–30 days from diagnosis. Baseline characteristics and clinical outcomes were compared up to two years from treatment. Results: 146 eyes of 146 patients were included. Sixty-eight patients were in the prompt anti-VEGF group, 31 in the intermediate anti-VEGF group, and 47 in the delayed anti-VEGF group. Following the induction phase of three intravitreal bevacizumab injections, the mean central subfield macular thickness (328.0 ± 115.4 µm vs. 364.6 ± 127.2 µm vs. 337.7 ± 150.1 µm, p = 0.432) and the best-corrected visual acuity (0.47 ± 0.38 vs. 0.59 ± 0.48 vs. 0.47 ± 0.44 logMAR units, p = 0.458) were comparable between the prompt, intermediate and delayed anti-VEGF groups. Anatomical and functional outcomes, treatment burden, number of relapses and eyes with second-line anti-VEGF therapy were comparable between the groups at both 1-year and 2-year timepoints. Conclusions: Our real-world evidence data emphasize that even if anti-VEGF induction cannot be initiated promptly within ten days from diagnosis of naïve exudative AMD, the visual and anatomical prognosis of the patients may not worsen if the treatment is started within one month of diagnosis. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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13 pages, 868 KiB

Open AccessArticle

Subclinical Ocular Changes after Intravitreal Injections of Different Anti-VEGF Agents for Neovascular Age-Related Macular Degeneration

by Hisashi Matsubara, Ryunosuke Nagashima, Shinichiro Chujo, Yoshitsugu Matsui, Kumiko Kato, Manami Kuze and Mineo Kondo

J. Clin. Med. 2023, 12(23), 7401; https://doi.org/10.3390/jcm12237401 - 29 Nov 2023

Cited by 2 | Viewed by 1946

Abstract

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) [...] Read more.

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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9 pages, 1070 KiB

Open AccessArticle

Clinical Characteristics of Eyes with Neovascular Age-Related Macular Degeneration and Retinal Pigment Epithelium Tears

by Junya Nagata, Satomi Shiose, Keijiro Ishikawa, Takuma Fukui, Kumiko Kano, Kenichiro Mori, Takahito Nakama, Shoji Notomi and Koh-Hei Sonoda

J. Clin. Med. 2023, 12(17), 5496; https://doi.org/10.3390/jcm12175496 - 24 Aug 2023

Cited by 3 | Viewed by 1392

Abstract

Background: Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help [...] Read more.

Background: Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help predict their occurrence before anti-VEGF therapy initiation. Methods: This study retrospectively analyzed neovascular age-related macular degeneration (nAMD) patients who visited the Kyushu University Hospital and started anti-VEGF therapy between April 2013 and June 2020. Using medical records, we collected the clinical data of patients with RPE tears, including age, sex, best-corrected visual acuity (BCVA), number of anti-VEGF drug injections and the type and size of pigment epithelial detachment (PED). Results: RPE tears occurred in 16 (1.50%) eyes of 16 patients in all 1068 nAMD eyes of 987 patients. The mean age of these patients with RPE tear was 81.7 ± 8.7 years. Fifteen eyes had typical AMD and one eye had polypoidal choroidal vasculopathy. The mean number of anti-VEGF drug injections before RPE tears was 5.0 ± 5.1. All patients experienced PED before the RPE tear (hemorrhagic, 4 eyes; serous vascular, 2 eyes; fibrovascular, 10 eyes). The average PED height and area were 615.7 ± 175.3 μm and 21.0 ± 7.2 mm², respectively. The sub-RPE cleft was observed in 10 eyes. The logMAR BCVA immediately after the RPE tear (0.73 ± 0.40) at 6 months (0.86 ± 0.51) and 12 months (0.84 ± 0.43) after the RPE tear were significantly worse than that before the RPE tear (0.58 ± 0.31; p < 0.05). The BCVA of patients with RPE tears that spread to the fovea was poorer than that of patients without RPE tears. Conclusions: In patients with nAMD, RPE tears tended to occur in typical AMD eyes with high or large PEDs, and sub-RPE clefts. The visual prognosis depended on whether the RPE tear included the fovea. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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12 pages, 917 KiB

Open AccessArticle

Prevalence of Geographic Atrophy in Advanced Age-Related Macular Degeneration (AMD) in Daily Practice

by Alaa Din Abdin, Machteld Devenijn, Roxana Fulga, Achim Langenbucher, Berthold Seitz and Hakan Kaymak

J. Clin. Med. 2023, 12(14), 4862; https://doi.org/10.3390/jcm12144862 - 24 Jul 2023

Cited by 8 | Viewed by 2974

Abstract

Purpose: To investigate the prevalence of geographic atrophy (GA) in advanced age-related macular degeneration (AMD) and the proportion of eyes that would meet the indication criteria for treatment with the first intravitreal anti-C3 agent (pegcetacoplan). Methods: This retrospective cross-sectional study included all AMD [...] Read more.

Purpose: To investigate the prevalence of geographic atrophy (GA) in advanced age-related macular degeneration (AMD) and the proportion of eyes that would meet the indication criteria for treatment with the first intravitreal anti-C3 agent (pegcetacoplan). Methods: This retrospective cross-sectional study included all AMD patients who visited the Macular-Retina-Centre Oberkassel in 2021. Eyes were classified according to AMD stages. Eyes with GA were divided into two groups regarding foveal involvement. Baseline factors were compared between eyes with foveal GA (FGA) and eyes with non-foveal GA (NFGA) to identify predictive factors for foveal involvement. Results: A total of 2033 eyes from 1027 patients were included. AMD stage was early in 296 (14.5%) cases, intermediate in 368 (18.1%) cases, and advanced in 1249 (61.4%) cases. A total of 1204 (60%) eyes had GA [932 (77%) FGA and 272 (23%) NFGA], while 125 eyes (27.4% from eyes with advanced dry AMD) met the indication criteria for treatment with intravitreal pegcetacoplan. The proportion of eyes with neovascular AMD was significantly higher in the FGA group compared to the NFGA group [598 (64.2%) vs. 152 (55.8%), p = 0.01]. Conclusions: At least a quarter of eyes with advanced AMD would be suitable for the upcoming intravitreal pegcetacoplan therapy. Foveal involvement of GA in advanced AMD seems to be more likely in neovascular AMD than in dry AMD. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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14 pages, 2817 KiB

Open AccessArticle

Long-Term Prognosis of Patients with Polypoidal Choroidal Vasculopathy Treated with Photodynamic Therapy

by Yukinori Sakaeda, Aki Kato, Soichiro Kuwayama, Shuichiro Hirahara, Norihiro Suzuki, Yuichiro Ogura, Yoko Nakazawa and Tsutomu Yasukawa

J. Clin. Med. 2023, 12(14), 4707; https://doi.org/10.3390/jcm12144707 - 16 Jul 2023

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Abstract

We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual [...] Read more.

We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), anatomical findings (vision-threatening findings), and treatment history were assessed. In total, 38 eyes underwent PDT as the initial treatment (initial PDT group) and 22 eyes underwent PDT as a rescue treatment (rescue PDT group). In the initial PDT group, 11 eyes (29%) did not require additional therapy throughout the observation period and maintained good BCVA. A total of 27 eyes (71%) underwent additional treatments and the mean BCVA was only stabilized for 2 years; thereafter, decreased vision occurred even with additional treatments. In the rescue PDT group, 22 eyes (95%) required additional treatment. Hard exudate, serous pigment epithelial detachment, and the total vision-threatening score were related to worse BCVA. Initial PDT may be effective in about 30% of cases with preservation of good vision and no need for additional treatment. However, patients with received rescue PDT needed additional treatment in most cases and the vision decreased in many cases. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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Review

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29 pages, 5960 KiB

Open AccessReview

Summary of the Therapeutic Options for Patients with Dry and Neovascular AMD

by Dorota Śpiewak, Łukasz Drzyzga, Mariola Dorecka and Dorota Wyględowska-Promieńska

J. Clin. Med. 2024, 13(14), 4227; https://doi.org/10.3390/jcm13144227 - 19 Jul 2024

Cited by 2 | Viewed by 2311

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have [...] Read more.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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13 pages, 1640 KiB

Open AccessReview

Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response

by Norimitsu Ban, Ari Shinojima, Kazuno Negishi and Toshihide Kurihara

J. Clin. Med. 2024, 13(9), 2608; https://doi.org/10.3390/jcm13092608 - 29 Apr 2024

Cited by 3 | Viewed by 1639

Abstract

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the [...] Read more.

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration)

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