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1.
J Gen Fam Med ; 25(3): 154-157, 2024 May.
Article in English | MEDLINE | ID: mdl-38707704

ABSTRACT

A 38-year-old pathologist developed multiple evanescent white dot syndrome (MEWDS). He documented his visual impairment in detail utilizing a light microscope for pathological diagnosis. Notably, the subjective defects illustrated by the patient were in good spatiotemporal agreement with diagnostic outcomes. The present report enhances the understanding of visual impairment associated with MEWDS through a comparative analysis of subjective experiences and objective clinical findings.

2.
Sci Rep ; 14(1): 11681, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38778065

ABSTRACT

This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 µm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications.


Subject(s)
Visual Acuity , Humans , Male , Female , Aged , Japan , Retrospective Studies , Aged, 80 and over , Visual Acuity/drug effects , Treatment Outcome , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/administration & dosage , Macular Degeneration/drug therapy , Macular Degeneration/pathology , Intravitreal Injections , Middle Aged , Tomography, Optical Coherence
3.
Jpn J Ophthalmol ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795194

ABSTRACT

PURPOSE: To investigate changes in the ocular surface and subjective symptoms during a three months administration of 3% diquafosol long-acting (DQL) eye drops. STUDY DESIGN: Prospective observational study. METHODS: DQL eye drops were administered as the sole treatment for all patients, including those in the group where DQL eye drops were newly prescribed (New DQL) and the group who switched from 3% diquafosol (DQS) eye drops (Switched DQL) in this prospective study. Each group underwent assessment of tear meniscus height (TMH), ocular surface disease index (OSDI), fluorescein break-up time (FBUT), fluorescein score, and Schirmer 1 test before DQL administration, at one month, and at three months. Changes in ocular surface scores and subjective symptoms at each time point were analyzed. RESULTS: The study included a total of 63 eyes of 63 patients, with a mean age of 60.3 ±14.6 (SD). Among them, 29 patients (20 women) were in the New DQL group, and 34 patients (24 women) were in the Switched DQL group. Both the New DQL and Switched DQL groups showed significant improvements in TMH, OSDI, FBUT, Fluorescein Score, and Schirmer 1 test after three months of DQL eye drop administration. CONCLUSION: DQL eye drops have the potential to improve ocular scores and subjective symptoms in patients with DE over a three months period, regardless of whether it is newly initiated or as a switch from DQS eye drops.

4.
Jpn J Ophthalmol ; 68(3): 211-215, 2024 May.
Article in English | MEDLINE | ID: mdl-38609716

ABSTRACT

PURPOSE: To investigate the association between the arm-to-choroidal circulation time (ACT) on indocyanine green angiography (IA) and clinical profile in patients with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Single-center retrospective study. METHODS: We included 38 eyes of 38 patients with PCV diagnosed using multimodal imaging and did not undergo previous treatment. All patients were treated with monthly aflibercept injections for 3 months and treat-and-extend regimens for the subsequent 12 months. Posterior vortex vein ACT was assessed on the first visit using Heidelberg IA. The patients were divided into two groups: ACT ≥20 s (L group; eight eyes) and ACT <20 s (S group; 30 eyes). The clinical profiles before and after treatment were analyzed to assess associations with ACT. RESULTS: The mean ACT was 16.39±3.3 s (L group: 21.25±1.49 s, women:men=2:6, mean age: 77.3±6.5 years; S group: 15.10±2.17 s, women:men=7:23, mean age: 75.5±6.9 years). No significant difference was observed in the mean subfoveal choroidal thickness between the L and the S groups (176±75 µm vs. 230±79 µm, P=0.10). However, there were significant differences between the L and S groups in retinal fluid accumulation and hemorrhage recurrence (eight/eight eyes, 100% vs. 13/30 eyes, 43%, P<0.001), mean aflibercept injections (8.8±1.6 vs. 7.0±1.6, P<0.01) during the 12-month period, and the number of polypoidal lesions (1.8±0.7 vs. 1.3±0.5, P<0.05). CONCLUSION: Patients with PCV and ACT >20 s are more likely to experience exudative change recurrence in the retina during treatment because they have more polypoidal lesions.


Subject(s)
Choroid , Fluorescein Angiography , Fundus Oculi , Intravitreal Injections , Polyps , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Tomography, Optical Coherence , Visual Acuity , Humans , Female , Male , Retrospective Studies , Choroid/blood supply , Choroid/diagnostic imaging , Aged , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Polyps/diagnosis , Polyps/drug therapy , Polyps/physiopathology , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Indocyanine Green/administration & dosage , Follow-Up Studies , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/physiopathology , Coloring Agents/administration & dosage , Aged, 80 and over , Choroid Diseases/diagnosis , Choroid Diseases/drug therapy , Choroid Diseases/physiopathology , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Regional Blood Flow/physiology , Multimodal Imaging , Blood Flow Velocity/physiology , Polypoidal Choroidal Vasculopathy
5.
Ophthalmol Ther ; 13(4): 935-954, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38308746

ABSTRACT

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.

6.
Jpn J Ophthalmol ; 68(2): 91-95, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38316703

ABSTRACT

PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded. RESULTS: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery. CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.


Subject(s)
Glaucoma , Macular Degeneration , Humans , Angiogenesis Inhibitors , Glaucoma/drug therapy , Intraocular Pressure , Intravitreal Injections , Japan/epidemiology , Macular Degeneration/drug therapy , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins/therapeutic use , Retrospective Studies
7.
Sci Rep ; 14(1): 43, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38168536

ABSTRACT

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.


Subject(s)
Dry Eye Syndromes , Meibomian Gland Dysfunction , Female , Humans , Aged , Meibomian Glands , Tears , Complement Activation
8.
Graefes Arch Clin Exp Ophthalmol ; 262(1): 43-51, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37668741

ABSTRACT

PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified. CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.


Subject(s)
Antibodies, Bispecific , Macular Degeneration , Retinal Detachment , Wet Macular Degeneration , Humans , Treatment Outcome , Follow-Up Studies , Retrospective Studies , Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retinal Detachment/drug therapy , Tomography, Optical Coherence/methods , Macular Degeneration/diagnosis , Macular Degeneration/drug therapy , Angiogenesis Inhibitors/therapeutic use , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/drug therapy
9.
Retina ; 44(4): 714-722, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38016089

ABSTRACT

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.


Subject(s)
Antibodies, Monoclonal, Humanized , Macular Degeneration , Retinal Vasculitis , Uveitis , Female , Humans , Angiogenesis Inhibitors , Incidence , Inflammation , Intravitreal Injections , Japan , Retina , Risk Factors , Vision Disorders , Male
10.
Graefes Arch Clin Exp Ophthalmol ; 261(12): 3475-3480, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37615698

ABSTRACT

PURPOSE: Posterior vortex vein pulsation on Heidelberg indocyanine green angiography (HRA-IA) video is reported to indicate the presence of congestion in these vessels. This study aimed to determine the relationship between posterior vortex vein pulsation, choroidal thickness, and choroidal vascular hyperpermeability (CVH) in polypoidal choroidal vasculopathy (PCV). METHODS: Forty-three eyes of 43 patients who had not received previous treatment and were diagnosed with PCV using multimodal imaging were included and retrospectively investigated. On initial visit, presence or absence of pulsation in the posterior vortex vein was analysed using HRA-IA. Subfoveal choroidal thickness (SFCT) was assessed, and patients were divided into the SFCT ≥ 200 µm and < 200 µm (P and NP, respectively) groups. Presence or absence of CVH was investigated using IA in the late phase, and the associations between the three parameters were analysed. RESULTS: Posterior vortex vein pulsation was detected in 24/43 eyes (55%). There were 27 eyes in the P group (mean SFCT, 286 ± 48 µm) and 16 eyes in the NP group (mean SFCT, 143 ± 41 µm). Pulsation was detected in 10 eyes (37%) in the P group and 14 eyes (88%) in the NP group. Incidence of pulsation was significantly higher in the NP group (P < 0.05). There were 17 (40%) patients with CVH-13 (48%) and four (25%) in the P and NP groups, respectively (P = 0.1994). There was no correlation between the presence or absence of pulsation and CVH (P = 0.1994). CONCLUSION: Congestion of the vortex vein is potentially associated with the pathogenesis of PCV with a thin choroid.


Subject(s)
Choroidal Neovascularization , Polyps , Humans , Polypoidal Choroidal Vasculopathy , Choroidal Neovascularization/diagnosis , Fluorescein Angiography/methods , Retrospective Studies , Choroid/pathology , Tomography, Optical Coherence , Indocyanine Green/pharmacology , Polyps/diagnosis
11.
BMC Ophthalmol ; 23(1): 329, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37464366

ABSTRACT

PURPOSE: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery. METHODS: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array. RESULTS: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (≦ 10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001). CONCLUSIONS: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively.


Subject(s)
Cataract , Dry Eye Syndromes , Ophthalmology , Humans , Female , Aged , Prospective Studies , Dry Eye Syndromes/etiology , Tears/physiology , Cataract/complications , Complement Activation
12.
Sci Rep ; 13(1): 8747, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37253802

ABSTRACT

This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.


Subject(s)
Choroidal Neovascularization , Wet Macular Degeneration , Humans , Angiogenesis Inhibitors/adverse effects , Retrospective Studies , Japan , Choroidal Neovascularization/drug therapy , Wet Macular Degeneration/drug therapy , Intravitreal Injections , Tomography, Optical Coherence , Fluorescein Angiography
13.
Retina ; 43(6): 999-1004, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36696603

ABSTRACT

PURPOSE: We examined the effect of ranibizumab with or without laser photocoagulation on retinal sensitivity in eyes with branch retinal vein occlusion. METHODS: Prospective randomized control study. Thirty patients with branch retinal vein occlusion received intravitreal injection of ranibizumab in a monthly pro re nata regimen. Fifteen patients received ranibizumab monotherapy alone (monotherapy group). The remaining 15 patients received rescue laser therapy at 3 or 9 months (combined group). The retinal sensitivity was measured at 32 points within central 8°, and the average of the main occlusion side among the 16 upper or 16 lower points was defined as the affected area sensitivity. RESULTS: In comparing the monotherapy group and the combined group, the number of injections during the 12 months was 5.4 versus 4.9, the change in retinal thickness ( µ m) was -254 versus -197, the ETDRS letters of improvement was +18.3 versus +19.6, and the change in the affected area sensitivity (dB) was +7.1 versus +4.6. At 12 months, all these results were significantly improved compared with their respective baselines, but none of the differences between the two groups reached statistical significance. CONCLUSION: Retinal sensitivity at 12 months improved in both the monotherapy group and the combined group. The additional laser did not reduce the number of injections or further improve visual acuity nor did it affect retinal sensitivity.


Subject(s)
Laser Therapy , Macular Edema , Retinal Vein Occlusion , Humans , Ranibizumab/therapeutic use , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Angiogenesis Inhibitors/therapeutic use , Intravitreal Injections , Prospective Studies , Macular Edema/drug therapy , Vascular Endothelial Growth Factor A , Laser Coagulation/methods , Retina , Lasers
14.
Hum Mutat ; 43(12): 2251-2264, 2022 12.
Article in English | MEDLINE | ID: mdl-36284460

ABSTRACT

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.


Subject(s)
Cone-Rod Dystrophies , Macular Degeneration , Retinal Diseases , Humans , Exome Sequencing , Eye Proteins/genetics , East Asian People , Mutation , Pedigree , Cone-Rod Dystrophies/diagnosis , Cone-Rod Dystrophies/genetics , Retinal Diseases/genetics , Macular Degeneration/genetics , DNA Mutational Analysis
15.
Ophthalmol Sci ; 2(2): 100167, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36249678

ABSTRACT

Purpose: To investigate the association of risk alleles in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) with complement activation products in the aqueous humor in eyes with neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and pachychoroid neovasculopathy (PNV). Design: Prospective, comparative, observational study. Participants: Treatment-naïve patients with nAMD and cataract patients as controls. Methods: The study included 236 eyes of 236 patients with nAMD and 49 control eyes of 49 patients. Aqueous humor samples were collected from 67 eyes with drusen-associated nAMD, 72 eyes with PCV, 26 eyes with RAP, and 71 eyes with PNV before intravitreal anti-VEGF injection and cataract surgery in the 49 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, and C5a using a bead-based immunoassay. Genotyping of the ARMS2 A69S (rs10490924), CFH I62V (rs800292), and CFH Y402H (rs1061170) was performed using TaqMan genotyping. Main Outcome Measures: The levels of complement activation products (C3a, C4a, and C5a) in the aqueous humor in each genotype of ARMS2 and CFH. Results: The C3a level in the aqueous humor was significantly elevated (P = 0.006) in patients with nAMD and the ARMS2 A69S risk allele, whereas the levels of the complement activation products were not associated with CFH I62V and Y402H genotypes. Among the control eyes, no significant differences were seen in any complement activation products for all genetic polymorphisms. The levels of the complement activation products in the aqueous humor of eyes with the nAMD subtypes for each genetic polymorphism did not show significant differences. Conclusions: The C3a concentration in the aqueous humor was significantly higher in Japanese nAMD patients with the ARMS2 A69S risk allele, whereas it was not elevated in the patients with CFH I62V. Age-related maculopathy susceptibility 2 A69S polymorphism is strongly associated with local complement activation in nAMD patients.

16.
Sci Rep ; 12(1): 15130, 2022 09 06.
Article in English | MEDLINE | ID: mdl-36068250

ABSTRACT

We created three types of vessel models: vessel volume, surface, and line models from swept-source optical coherence tomography images and tested experimentally calculated three-dimensional (3D) biomarkers. The choroidal volume (CVolume), surface area (VSurface), and vessel length-associated index (VLI) were measured. The calculated 3D parameters were the mean choroidal thickness, choroidal vascularity index (CVI), vessel length density index (VLDI), vessel length to the stromal (VL-S) ratio, surface-to-volume ratio (S-V ratio), and vessel diameter index (VDI). Cluster analysis showed that the parameters were classified into two clusters: one was represented by the VVolume including the CVolume, VSurface, CVI, S-V ratio, VLI, VDI, and subfoveal choroidal thickness and the other by the VL-S ratio including the VLDI. Regarding the regional distribution, the VVolume, CVolume, VSurface, CVI, VLI, VL-S ratio, and VDI at the foveal center were higher than at the parafovea (P < 0.01). Although the VVolume decreased with age and axial length (AL) elongation, the association of the 3D parameters with age and AL elongation differed. The VLI, VLDI, VL-S ratio, and CVI decreased with age (P < 0.01) but not with AL elongation. The results suggested a structural difference in the choroidal vessel volume reduction between aging and AL elongation. The 3D parameters may provide additional information about the choroidal vasculature.


Subject(s)
Choroid , Tomography, Optical Coherence , Biomarkers , Choroid/blood supply , Choroid/diagnostic imaging , Fovea Centralis , Retinal Vessels , Tomography, Optical Coherence/methods
17.
Jpn J Ophthalmol ; 66(4): 379-385, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35595951

ABSTRACT

PURPOSE: To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study. STUDY DESIGN: Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated. RESULTS: Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P < 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases. CONCLUSIONS: IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.


Subject(s)
Antibodies, Monoclonal, Humanized , Choroid , Wet Macular Degeneration , Aged , Angiogenesis Inhibitors , Antibodies, Monoclonal, Humanized/therapeutic use , Choroid/blood supply , Female , Fluorescein Angiography/methods , Humans , Intravitreal Injections , Japan/epidemiology , Male , Retrospective Studies , Tomography, Optical Coherence/methods , Visual Acuity , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/drug therapy
18.
PLoS One ; 17(2): e0264703, 2022.
Article in English | MEDLINE | ID: mdl-35213672

ABSTRACT

PURPOSE: To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD. METHODS: Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters. RESULTS: Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86). CONCLUSION: The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.


Subject(s)
Choroidal Neovascularization/etiology , Eye/diagnostic imaging , Macular Degeneration/pathology , Optical Imaging , Age Factors , Aged , Aged, 80 and over , Dietary Supplements/adverse effects , Female , Follow-Up Studies , Humans , Japan , Lipoproteins, LDL/blood , Male , Multivariate Analysis , Prospective Studies
19.
Jpn J Ophthalmol ; 66(3): 213-226, 2022 May.
Article in English | MEDLINE | ID: mdl-35171356

ABSTRACT

The choroid is vascularized membranous tissue that supplies oxygen and nutrients to the photoreceptors and outer retina. Choroidal vessels underlying the retinal pigment epithelium are difficult to visualize by ophthalmoscopy and slit-lamp examinations. Optical coherence tomography (OCT) imaging made significant advancements in the last 2 decades; it allows visualization of the choroid and its vasculature. Enhanced-depth imaging techniques and swept-source OCT provide detailed choroidal images. A recent breakthrough, OCT angiography (OCTA), visualizes blood flow in the choriocapillaris. However, despite using OCTA, it is hard to visualize the choroidal vessel blood flow. In conventional structural OCT the choroidal vessel structure appears as a low-intensity objects. Image-processing techniques help obtain structural information about these vessels. Manual or automated segmentation of the choroid and binarization techniques enable evaluation of choroidal vessels. Viewing the three-dimensional choroidal vasculature is also possible using high-scan speed volumetric OCT. Unfortunately, although choroidal image analyses are possible using the images obtained by commercially available OCT, the built-in function that analyzes the choroidal vasculature may be insufficient to perform quantitative imaging analysis. Physicians must do that themselves. This review summarizes recent choroidal imaging processing techniques and explains the interpretation of the results for the benefit of imaging experts and ophthalmologists alike.


Subject(s)
Choroid Diseases , Tomography, Optical Coherence , Choroid/blood supply , Choroid Diseases/diagnosis , Fluorescein Angiography/methods , Humans , Retinal Pigment Epithelium , Tomography, Optical Coherence/methods
20.
Graefes Arch Clin Exp Ophthalmol ; 260(6): 1857-1865, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35034215

ABSTRACT

BACKGROUND/PURPOSE: Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD. METHODS: This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography. RESULTS: The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P < 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 µm at baseline to 216.9 ± 110.2 µm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group. CONCLUSION: Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.


Subject(s)
Angiogenesis Inhibitors , Wet Macular Degeneration , Antibodies, Monoclonal, Humanized , Choroid , Fluorescein Angiography/methods , Humans , Intravitreal Injections , Retrospective Studies , Tomography, Optical Coherence/methods , Vascular Endothelial Growth Factor A , Visual Acuity , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/drug therapy
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