One-year outcomes and safety assessment of faricimab in treatment-naïve patients with neovascular age-related macular degeneration in Japan.

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.

Efficacy of 3% diquafosol long-acting eye drops in dry eye patients treated for three months.

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.

Association between the arm-to-choroidal circulation time and clinical profile in patients with polypoidal choroidal vasculopathy.

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.

Intraocular pressure changes during intravitreal aflibercept injection based on treat-and-extend regimen in Japanese patients with neovascular age-related macular degeneration and glaucoma.

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.

Complement activation products in tears of dry eye and meibomian gland dysfunction.

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.

Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.

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.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

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.

Methane diffusion affects characteristics of benthic communities in and around microbial mat-covered sediments in the northeastern Japan sea.

We investigated relationships between features of benthic macrofaunal communities and geochemical parameters in and around microbial mat-covered sediments associated with a methane seepage on Sakata Knoll in the eastern Japan Sea. A depression on top of the knoll corresponds to a gas-hydrate-bearing area with seepage of methane-rich fluid, and microbial mats cover the seafloor sediments. Sediment cores were collected at three sites for this study: one within a microbial mat, a second a few meters outside of the microbial mat, and a third from a reference site outside the gas-hydrate-bearing areas. Morphological analysis showed that the site inside the microbial mat had higher macrofaunal density and biomass compared with the other sites. 18S rRNA gene analysis showed that annelids were dominant in the surface sediment inside the microbial mat with the possible occurrence of microbial anaerobic oxidation of methane (AOM), whereas in the surface sediments outside the microbial mat and at the reference site the predominant species belonged to phylum Cercozoa. Morphological analysis also showed that the surface sediment inside the microbial mat noticeably favored annelids, with dorvilleid Ophryotrocha sp. and ampharetid Neosabellides sp. identified as major constituents. Statistical analysis showed that sulfidic sediment conditions with concentrations of H2S up to 121 µM resulting from AOM likely resulted in the predominance of annelids with tolerance to sulfide. Both the 18S rRNA genes and macrofaunal characteristics showed that benthic biodiversity among the three sites was greatest outside the microbial mat. The site outside the microbial mat may represent geochemical transition conditions, including a lower rate of upward methane gas-flow compared with the site inside the microbial mat. The high biodiversity there might result from the presence of species specifically suited to the transition zone as well as species also found in photosynthesis-based communities of the background environment.

Relationship between pulsation of posterior vortex vein, choroidal thickness, and choroidal vascular hyperpermeability in polypoidal choroidal vasculopathy.

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.

Preliminary study on the acute effects of hydrogen sulfide on Amphipoda (Lysianassoidea; Pseudorchomene sp. and Anonyx sp.) collected from deep-sea floors in the Sea of Japan.

To study the environmental impact of the assessment technologies for the development of shallow methane hydrate zones in the Sea of Japan, deep-sea amphipods (Pseudorchomene sp. and Anonyx sp.) were collected from a depth of approximately 1000 m and were tested for H2S toxicity. At 0.57 mg L-1 H2S, all specimens of Pseudorchomene sp. were dead after 96 h, whereas all individuals survived at 0.18 mg L-1. Moreover, Anonyx sp. had a survival rate of 17 % after 96 h at 0.24 mg L-1. A similar toxicity test was conducted with the coastal amphipod Merita sp., a detritivore, and all individuals died within 24 h at 0.15 mg L-1. These results suggested that compared with coastal detritivorous amphipods, deep-sea detritivorous amphipods, which also live near biomats with sediment H2S concentrations exceeding 10 mg L-1, showed a higher tolerance to H2S.

Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan.

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.

Micro-abnormalities in the retina and choroid induced by anti-CTLA4 treatment.

Anti-Cytotoxic T-Lymphocyte Associated protein 4 agents, such as ipilimumab, are widely applied to various cancers. However, they cause immune-related adverse effects throughout the body, including the eye. This study examined whether ipilimumab induces retinal and choroidal abnormalities in rodents, and investigated potential underlying mechanisms. Female wild-type mice were injected with ipilimumab three times/week for 5 weeks. The mice underwent optical coherence tomography (OCT) on the first day of the 6th week. Retinal function and morphology were evaluated by light microscopy, immunohistochemistry and electroretinography (ERG). On OCT, the lines indicating the ellipsoid and interdigitation were obscure in treated mice, suggesting outer retina destruction. Haematoxylin-eosin staining revealed destruction, shortening, and outer segment vacuolization. Treated mice exhibited weaker, fragmented rhodamine peanut agglutinin staining in outer photoreceptor structures. The choroid of treated mice showed severe infiltration of CD45-positive cells. In addition, CD8-positive cells invaded into the outer retina. On ERG, rod, maximum responses of combined rods and cones, and cone response wave amplitudes were significantly reduced in treated mice. Ipilimumab may induce impairments in outer photoreceptor architecture accompanied with CD8- positive infiltration in the retina and CD45-positive cell infiltration in the choroid, which may contribute to retinal function deterioration.

Quadrant laser photocoagulation trial to ameliorate choroidal congestion in central serous chorioretinopathy.

PURPOSE: To investigate the efficacy and safety of quadrant laser photocoagulation to ameliorate the choroidal congestion in central serous choroidopathy (CSC). STUDY DESIGN: Historically controlled study. METHODS: We prospectively studied 20 eyes with acute CSC in the quadrant laser group, in which laser photocoagulation was applied to the macular leakage point(s) as well as the quadrant of the fundus showing vortex vein dilatation. Central choroidal thickness (CCT), vertical diameter of dilated vortex vein, resolution rate of serous retinal detachment (SRD), and visual field were evaluated post-treatment. We also compared the results with those of 18 retrospectively analyzed eyes with acute CSC in an external control group, in which laser photocoagulation had been applied only to the macular leakage point(s). RESULTS: In the quadrant laser group, 2 eyes were excluded from data analysis due to choroidal neovascularization (CNV). CCT was significantly reduced in both groups, but more significantly in the quadrant laser group. The vertical diameter of the dilated vortex vein was significantly decreased only in the quadrant laser group. The resolution rate of SRD was similar in the two groups. In the quadrant laser group, 8 eyes (44.4%) showed mild deterioration of the visual field, consistent with the area subjected to quadrant laser photocoagulation. CONCLUSION: Quadrant laser photocoagulation can have limited efficacy for ameliorating vortex vein congestion in CSC. When laser photocoagulation to the macular area is combined with quadrant laser photocoagulation, attention must be paid to the possible development of CNV and visual field deterioration.

Comparison of the 2-Year Results of Photodynamic Therapy with Aflibercept and Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy.

Purpose: To compare the efficacies of photodynamic therapy (PDT) combined with intravitreal aflibercept (IVA) injections and IVA monotherapy using a treat-and-extend regimen (TAE) for treatment-naïve polypoidal choroidal vasculopathy (PCV). Patients and Methods: One hundred and nine eyes treated with PDT combined with IVA (PDT+IVA group: 51 eyes) or IVA monotherapy (IVA group: 58 eyes) were assessed for 2 years. The main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of IVA injections, and macular atrophy (MA). Polypoidal lesions before and after the loading phase were assessed using indocyanine green angiography. Results: In both groups, BCVA significantly improved after the loading phase and was maintained for 2 years. CMT and CCT were significantly reduced in both groups, without significant differences after 2 years between the groups (P=0.2708). The mean number of IVA injections in the IVA and PDT+IVA groups during the 2 years were 13.2±3.3 and 12.7±1.8, respectively, without a significant difference (P=0.06). The frequencies of MA expansion in the IVA and PDT+IVA groups during the 2 years were 25.9% and 33.4%, respectively, with no significant difference in the incidence (odds ratio: 1.40, P=0.4253). The ratios of polyp regression after the loading phase in the IVA and PDT+IVA groups were 55.2% and 94.1%, respectively, with a significant difference (P<0.0001). Conclusion: PDT combined with IVA injections using a TAE regimen is effective for anatomical and visual function improvement, without a significant difference as compared to IVA monotherapy. It can facilitate complete regression of polyps with higher odds.

Comparison of the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment.

BACKGROUND: To compare the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment (PED) in age-related macular degeneration. METHODS: Eighty-three eyes of 83 patients diagnosed with type 1 macular neovascularization were included and retrospectively analysed using multimodal imaging. Forty-nine eyes were treated with intravitreal aflibercept injections (IVA group), and 34 eyes were treated with brolucizumab (IVBr group), with three consecutive injections administered as induction therapy. Before treatment and 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, MH at baseline (228 ± 169 µm) diminished to 180 ± 150 (P = 0.2558), 165 ± 140 (P = 0.0962), and 150 ± 129 µm (P = 0.0284) at 1, 2, and 3 months after treatment, respectively; the reduction at 3 months was significant. In contrast, in the IVBr group, the MH was 307 ± 254 µm before treatment, and it decreased to 183 ± 156 µm (P = 0.0113), 139 ± 114 µm (P = 0.0003), and 125 ± 126 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively, and the reduction at 1 month was significant. In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of PED after IVBr treatment regressed faster than that after IVA treatment.

Vortex vein congestion in the monkey eye: A possible animal model of pachychoroid.

PURPOSE: To create vortex vein congestion in the monkey eye as a possible pachychoroid model. METHODS: We ligated superotemporal and inferotemporal vortex veins at the surface of the sclera in monkey eyes. Optical coherence tomography (OCT) and indocyanine green angiography (ICGA) were performed before and 2, 7, and 28 days after the vortex vein ligations to investigate changes in vortex vein morphology and alterations in choroidal blood flow. RESULTS: Before the vortex vein ligations, en face OCT and ICGA images showed well organized vortex veins as well as horizontal and vertical watershed zones. Two days after the vortex vein ligations, dilatation of the superotemporal and inferotemporal vortex veins as well as intervortex venous anastomoses were seen on en face OCT and ICGA images. B-mode OCT images showed choroidal thickening associated with dilatation of the outer choroidal vessels. Moreover, video ICGA revealed choriocapillaris filling delay and pulsatile flow in the dilated vortex veins. At 7 and 28 days after we ligated the vortex veins, these findings were reduced, except for the intervortex venous anastomoses. CONCLUSIONS: We created a monkey model of vortex vein congestion by ligating two vortex veins. This animal model demonstrated pachychoroid-related findings, indicating that vortex vein congestion is involved in the pathogenesis of pachychoroid. However, remodeling of the choroidal drainage route via intervortex venous anastomosis appeared to compensate for the vortex vein congestion created in this model.

Occlusion of a Vortex Vein After Treatment With Half-Fluence Photodynamic Therapy Combined With Intravitreal Aflibercept Injection for Pachychoroid Neovasculopathy.

Photodynamic therapy (PDT) is a treatment option for pachychoroid diseases such as central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), and peripapillary pachychoroid syndrome (PPS). On the other hand, morphological changes of choroidal vessels in the irradiated field after PDT have also been discussed, with occlusion of choriocapillaris and stenosis of choroidal middle and large vessels being reported. Here, we report a case of vortex vein occlusion after half-fluence PDT (HF-PDT) combined with an anti-vascular endothelial growth factor (VEGF) agent for PNV. In this case, HF-PDT achieved complete occlusion of PNV; in addition, a vortex vein that flowed in PNV but was located outside the PDT irradiation field was fully occluded three months post-treatment. At the occluded site of the vortex vein, indocyanine green video angiography revealed pulsation downstream of the vortex vein. Such occlusion of a large vessel by HF-PDT has not been reported previously. Occlusion could be induced by two factors: the potentiality of PDT and risk factors for thromboembolism, such as older age, smoking, and arrhythmia. Further studies are required to determine the mechanisms of these large vessel occlusions.

Intravitreal Aflibercept versus Brolucizumab for Treatment-Naive Neovascular Age-Related Macular Degeneration with Type 1 Macular Neovascularization: Comparison of Short-Term Outcomes.

INTRODUCTION: The purpose of this study was to evaluate the outcomes of loading-phase treatment with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (nAMD) associated with type 1 macular neovascularization (MNV). METHODS: We retrospectively studied 108 consecutive eyes undergoing IVA and 103 consecutive eyes administered IVBr. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), dry macula achievement, polypoidal lesion regression, and development of intraocular inflammation (IOI) were all assessed. RESULTS: During the loading-phase treatment, IOI was detected in 18 eyes (17.5%) in the IVBr but none of those in the IVA group (p < 0.01). The loading-phase treatment was completed in 101 eyes in the IVA and 85 eyes in the IVBr group. In those cases, BCVA improved significantly, and CMT and CCT showed significant reductions after the loading-phase treatment in both groups (all p < 0.01). The CCT reduction was significantly greater with IVBr than with IVA (32 ± 28 µm vs. 40 ± 25 µm, p < 0.01). The dry macula achievement rate was significantly higher in the IVBr than in the IVA group (71.3 vs. 85.9%, p < 0.05). We observed complete regression of polypoidal lesions significantly more frequently with IVBr than with IVA (47.5 vs. 77.3%, p < 0.01). DISCUSSION/CONCLUSION: Loading-phase treatment with IVA or IVBr for treatment-naïve nAMD with type 1 MNV effectively improved BCVA and diminished exudative changes. The CCT reduction, dry macula achievement, and polypoidal lesion regression rates were all significantly greater in the IVBr than in the IVA group. The incidence of IOI was significantly higher with IVBr than with IVA.

Lacrimal Duct Obstruction and Infection Associated with Non-Traumatic Corneal Perforation: A Case Series.

Purpose: To report a case series of lacrimal duct obstruction and infection associated with non-traumatic corneal perforation. Case Series: This study included 6 eyes in 6 patients with non-traumatic corneal perforation treated between April 2019 and March 2021. All 6 cases were associated with lacrimal duct obstruction and infection. Purulent discharge caused by lacrimal duct infection was observed in all 6 patients (100%). However, three of the 6 patients (50%) did not show purulent discharge at initial examination and lacrimal duct obstruction was therefore not initially recognized. Dry eye was observed in five of the 6 patients (83%) and may have caused corneal deterioration, increasing susceptibility to perforation. Further, dry eye masks symptoms of lacrimal duct obstruction and infections, such as epiphora and regurgitation of purulent discharge, making the association with lacrimal duct obstruction and infection difficult to determine. All patients were treated for both corneal perforation and lacrimal duct disease, and conditions improved, with no recurrence of either corneal perforation or lacrimal duct disease. Conclusion: In patients with a combination of lacrimal duct disease and corneal perforation, treatment of both diseases resulted in stabilization of patient condition. Dry eyes may mask symptoms of lacrimal duct diseases, such as epiphora and purulent discharge, and lacrimal duct disease may thus be underdiagnosed.

One-year results of treat-and-extend regimen with intravitreal brolucizumab for treatment-naïve neovascular age-related macular degeneration with type 1 macular neovascularization.

We evaluated 1-year outcomes of loading phase treatment followed by maintenance treatment using a treat-and-extend (TAE) regimen with intravitreal brolucizumab for neovascular age-related macular degeneration (nAMD) associated with type 1 macular neovascularization (MNV). We analyzed 68 eyes of 65 consecutive patients with treatment-naïve nAMD associated with type 1 MNV. Forty-five eyes (66.2%) completed the 1-year treatment with intravitreal brolucizumab. In those cases, best-corrected visual acuity (BCVA) showed significant improvement, while there were significant reductions in foveal thickness and central choroidal thickness, after the initial brolucizumab injection, which were maintained until the last visit. The average total number of injections over 1 year was 6.4 ± 0.6. The average intended injection interval at the last visit was 14.0 ± 2.9 weeks. Moreover, 17of 23 eyes (73.9%) with polypoidal lesions showed complete regression of these lesions after the loading phase treatment. Although intraocular inflammation (IOI) was observed in 15 of 68 eyes (22.1%) within 1 year, amelioration in response to combination therapy with topical and subtenon injection of steroids, without visual decline, was obtained. These results indicate that loading phase treatment followed by the TAE regimen with intravitreal brolucizumab might improve BCVA and ameliorate exudative changes in eyes with treatment-naïve nAMD associated with type 1 MNV. Moreover, intravitreal brolucizumab can potentially reduce the treatment burden of nAMD. Prompt steroid therapy might be efficacious for ameliorating brolucizumab-related IOI without visual decline.