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

PURPOSE: To evaluate 1-year outcomes of loading phase treatment followed by maintenance therapy using a treat-and-extend (TAE) regimen with intravitreal faricimab for neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective, interventional case series. METHODS: We retrospectively studied 40 eyes of 38 consecutive patients with treatment-naïve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit. RESULTS: Thirty eyes (75.0%) had completed the 1-year intravitreal faricimab treatment. Their BCVA showed significant improvement, with significant reductions in foveal thickness and CCT. The total number of injections during the 1-year treatment period was 6.6 ± 0.7. The intended injection interval at the last visit was 12.7 ± 3.3 weeks. Of the 10 eyes (25.0%) failing to complete the 1-year faricimab treatment, 1 eye developed intraocular inflammation after the loading phase treatment but showed no recurrence of exudative changes, and no further treatment was required. Moreover, 5 eyes switched to intravitreal brolucizumab injection due to persistent exudative changes with an 8-week interval of faricimab injections. The remaining 4 eyes either dropped out or the patient died. CONCLUSIONS: A loading phase treatment followed by a TAE regimen with intravitreal faricimab appears to be generally safe and effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of faricimab every 8 weeks in the maintenance phase.

Predicting treatment outcomes of intravitreal brolucizumab for polypoidal choroidal vasculopathy through noninvasive assessment of polypoidal lesion blood flow with optical coherence tomography angiography.

We investigated the assessment of blood flow within polypoidal lesions using optical coherence tomography angiography (OCTA) to determine intravitreal brolucizumab (IVBr) efficacy for treating polypoidal choroidal vasculopathy (PCV). We retrospectively studied 46 eyes with PCV that completed 1-year IVBr treatment. Blood flow signals within polypoidal lesions were evaluated using OCTA after loading-phase treatment, and 1-year outcomes were compared between eyes in which blood flow signals disappeared versus persisting. After loading-phase treatment, blood flow signals within polypoidal lesions disappeared in 31 eyes and persisted in 15. In the former group, visual acuity improved significantly throughout the year (P < 0.01), while in the latter there was no significant difference between baseline and after 1 year. The total number of injections was significantly lower with than without disappearance of blood flow signals (6.0 vs. 6.9, P < 0.01). The intended injection interval at the last visit was significantly longer in the former than in the latter group (15.7 weeks vs. 12.5 weeks, P < 0.01). These results indicate that PCV cases showing disappearance of blood flow signals within polypoidal lesions by OCTA after loading-phase treatment had favorable 1-year outcomes of IVBr. Therefore, evaluating blood flow within polypoidal lesions by OCTA may allow noninvasive prediction of PCV treatment outcomes.

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.

Attenuation of irradiated choroid and its regional vortex veins in central serous chorioretinopathy after photodynamic therapy.

We retrospectively studied 12 eyes of 12 patients with central serous chorioretinopathy (CSC) to investigate choroidal thickness changes following half-fluence photodynamic therapy (PDT) using widefield choroidal thickness maps obtained by optical coherence tomography (OCT). Additionally, we assessed the relationship between choroidal thickness changes and the regional vortex veins as visualized on widefield en face OCT of the choroid. Pre-treatment en face images of the choroidal vasculature were superimposed on subtracted choroidal thickness maps before and 3 months after half-fluence PDT. The choroidal thickness decreased mainly in the irradiated macular area and in the region of vortex veins which function as drainage for the macula in all eyes. Eleven eyes (91.7%) showed choroidal thinning in the nasal area which overlapped with the nasal vortex vein distribution. Moreover, in 10 (90.9%) of those eyes, we observed intervortex venous anastomosis across the vertical watershed zone. Quantitative analysis revealed that the reduction in choroidal thickness was most pronounced in the macular area. Furthermore, the choroidal thickness reduction in the area with macular drainage vortex veins was significantly greater than that in the area without such vortex veins. These results suggest that half-fluence PDT might decrease choroidal thickness due to choriocapillaris occlusion in the irradiated macula, possibly leading to diminished venous drainage from the macula to regional vortex veins. Moreover, venous blood flow through the anastomotic vessels from the macular drainage vortex veins into the nasal vortex veins might be reduced post-treatment.

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.

Short-term outcomes of intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and safety of loading phase treatment with 3 monthly intravitreal injections of faricimab for neovascular age-related macular degeneration (nAMD). METHODS: We retrospectively analyzed 16-week outcomes of 40 consecutive eyes of 38 patients with treatment-naïve nAMD. Three monthly injections of faricimab were administered to all eyes as a loading phase treatment. Best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), and dry macula achievement were all assessed every 4 weeks. Moreover, the regression of polypoidal lesions was evaluated after the loading phase. RESULTS: BCVA was 0.33 ± 0.41 at baseline and showed significant improvement to 0.22 ± 0.36 at week 16 (P < 0.01). Foveal thickness was 278 ± 116 µm at baseline, decreasing significantly to 173 ± 48 µm at week 16 (P < 0.01). CCT was 214 ± 98 µm at baseline, decreasing significantly to 192 ± 89 µm at week 16 (P < 0.01). Dry macula was achieved in 31 eyes (79.5%) at week 16. Indocyanine green angiography after the loading phase revealed complete regression of polypoidal lesions in 11 of 18 eyes (61.1%) with polypoidal lesions. One eye (2.5%) developed vitritis without visual loss at week 16. CONCLUSION: Loading phase treatment with intravitreal faricimab appears to generally be safe and effective for improving visual acuity and reducing exudative changes in eyes with nAMD.

RETINAL VASCULITIS OR VASCULAR OCCLUSION AFTER BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Systematic Review of Real-World Evidence.

PURPOSE: Retinal vasculitis or vascular occlusion (RV/RO) have been reported after brolucizumab for neovascular age-related macular degeneration. This systematic literature review evaluated RV/RO events after brolucizumab in real-world practice. METHODS: Systematic literature searches identified 89 publications; 19 were included. RESULTS: Publications described 63 patients (70 eyes) with an RV/RO event following brolucizumab. Mean age was 77.6 years and 77.8% of patients were women; 32 eyes (45.7%) received one brolucizumab injection before RV/RO. Mean (range) time to event from last brolucizumab injection was 19.4 (0-63) days, with 87.5% of events occurring within 30 days. Among eyes with preevent and postevent visual acuity (VA) assessments, 22/42 eyes (52.4%) showed unchanged (±0.08 logMAR) or improved vision from last recorded preevent assessment at latest follow-up, whereas 15/42 eyes (35.7%) showed ≥0.30 logMAR (≥15 letters) VA reduction. Patients with no VA loss were on average slightly younger and had a higher proportion of nonocclusive events. CONCLUSION: Most RV/RO events reported after brolucizumab in early real-world practice occurred in women. Among eyes with VA measurements, approximately half experienced VA loss; overall, about one-third had VA reduction of ≥0.30 logMAR at latest follow-up, with indications of regional variations.

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.

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

We previously reported one-year results of a treat-and-extend (TAE) regimen with intravitreal brolucizumab for 68 eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) associated with type 1 macular neovascularization (MNV). In the current study, we evaluated second-year results of the brolucizumab TAE therapy in 45 eyes with type 1 MNV that had completed the first-year treatment. Forty-three eyes (95.6%) received brolucizumab TAE treatment during a period of 96 weeks. The significant improvement of best-corrected visual acuity in the first year was maintained in the second year. Moreover, the significant foveal thickness and central choroidal thickness reductions in the first year were maintained in the second year. The total number of injections over the 96-week study period was 10.0 ± 1.4, with 6.4 ± 0.6 in the first year and 3.6 ± 1.0 in the second year. The intended injection interval at week 96 was 8 weeks in 9 eyes (20.9%), 12 weeks in 3 eyes (7.0%), and 16 weeks in 31 eyes (72.1%), with an average injection interval of 14.0 ± 3.3 weeks. No eyes developed brolucizumab-related intraocular inflammation (IOI) during the second-year treatment. These results indicate that the TAE regimen with intravitreal brolucizumab for treatment-naïve nAMD associated with type 1 MNV effectively maintained the improved visual acuity and the diminished exudative changes in the second year. Moreover, intravitreal brolucizumab has the potential to reduce the treatment burden of nAMD. The risk of developing brolucizumab-related IOI appeared to be very low during the second year of this TAE regimen.

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.

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.

Relationship between Pachychoroid and Polypoidal Choroidal Vasculopathy.

Previous clinical studies have suggested that pachychoroid can induce macular neovascularization (MNV) to develop pachychoroid neovasculopathy (PNV) and that PNV can progress to polypoidal choroidal vasculopathy (PCV). Recent studies based on the pachychoroid concept are now gradually revealing the true nature of, at least some part of, PCV. However, previous studies on PNV and/or PCV have used different frameworks for the classification of PNV, PCV, and neovascular age-related macular degeneration (nAMD). These have hampered the rapid overhaul of the understanding of PCV. Some investigators have assumed that all PCV is pachychoroid-driven whereas other investigators have classified PCV into "pachychoroid PCV" and "non-pachychoroid PCV". Furthermore, since there is no consensus as to whether PNV includes PCV, some studies have included PCV with PNV, while other studies have excluded PCV from PNV. To address these gaps, we summarize previous studies on PCV and pachychoroid. Even before the proposal of the pachychoroid concept, previous studies had suggested that PCV could be divided into two subtypes, of which one was characterized by pachychoroid features. Previous studies had also provided keys to understand relationship between PCV and PNV. We here recommend a refined conceptual framework for future studies on PNV, PCV, and nAMD. Considering the current inconsistent understanding of PCV, we should be cautious about using the term PCV until we understand the true nature of PCV.

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.

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.

A new insight into pachychoroid diseases: Remodeling of choroidal vasculature.

PURPOSE: Pachychoroid spectrum diseases are regarded as being different manifestations of a common pathogenic process. We suggest that pachychoroid diseases are consequences of chronic vortex vein stasis. METHODS: We describe how we came to this conclusion based on our own recent reports as well as a search of the related literature. RESULTS: Central serous chorioretinopathy (CSC) is the first stage of pachychoroid spectrum diseases. CSC is caused by congestion of choroidal veins, which are branches of the vortex veins. The venous outflow tract of the choroid is divided into four quadrants, based on horizontal and vertical watershed zones, with one or two vortex veins in each quadrant being independently responsible for venous outflow. In acute CSC, vortex vein stasis frequently causes asymmetric dilatation of the vortex veins in the horizontal watershed. The area of geographic filling delay in the choriocapillaris coincides with the area of this asymmetrically dilated vortex veins. With chronic stasis of the vortex veins, venous anastomosis occurs in the watershed zone as a means of compensating for the stasis, and the choriocapillaris becomes occluded in the area of filling delay. The anastomotic vessels dilate, becoming often hyperpermeable, and are then recognizable as pachyvessels. With the development of choriocapillaris ischemia, choroidal neovascularization (CNV) occurs at the site of pachyvessels. This is termed pachychoroid neovasculopathy (PNV). Polypoidal choroidal vasculopathy is regarded as a variant of PNV. CONCLUSIONS: Intervortex venous anastomosis is among the key factors underlying the development of pachychoroid diseases. Remodeling of the venous drainage route though the anastomosis across the watershed zones is apparently a common response to chronic vortex vein stasis.

Clinical characteristics and pachychoroid incidence in Japanese patients with neovascular age-related macular degeneration.

The phenotypes of neovascular age-related macular degeneration (nAMD) are recognized as differing between Caucasian and Asian patients. Pachychoroid is thought to be more prevalent in Asians than in Caucasians, and may be involved in the development of nAMD in Asian patients. Therefore, we investigated the clinical characteristics and pachychoroid incidence in Japanese patients with nAMD. We retrospectively analyzed 385 eyes of 370 consecutive Japanese patients with treatment naïve nAMD. According to the nAMD nomenclature, type 1 macular neovascularization (MNV) was observed in 132 eyes (34.3%), polypoidal choroidal vasculopathy (PCV) in 137 (35.6%), mixed type 1 and type 2 MNV in 32 (8.3%), type 2 MNV in 43 (11.2%), and type 3 MNV in 41 (10.6%). Pachychoroid was seen in 58.3% of type 1 MNV, 75.2% of PCV, 34.4% of mixed type 1 and type 2 MNV, 14.0% of type 2 MNV, and 0% of type 3 MNV. Compared to nAMD patients without pachychoroid (188 eyes), those who had nAMD with pachychoroid (197 eyes) were significantly younger, had a higher proportion of males, greater central choroidal thickness, and a higher frequency of macular vortex vein anastomoses (all P < 0.001). Furthermore, drusen subtypes differed significantly between the two groups (P < 0.001). These results suggest that most Japanese nAMD patients might have type 1 MNV or PCV. Moreover, in approximately half of patients, nAMD might be associated with pachychoroid, and choroidal congestion may be involved in the development of MNV in these cases.

Choroidal alterations during the clinical course of commotio retinae.

PURPOSE: To analyse the alterations in the choroidal structure of eyes with commotio retinae due to blunt-force trauma. METHODS: This retrospective study included 51 eyes of 50 patients who underwent swept-source optical coherence tomography (SS-OCT) during their initial visit and throughout their clinical course between March 2013 and February 2020. MAIN OUTCOMES AND MEASURES: This study focused on four choroidal measures: comparison of central choroidal thickness (CCT) between the injured and contralateral eyes immediately after injury, changes in the CCT, ratio of choroidal luminal and stromal properties in the injured eye during the clinical course and change in the suprachoroidal structure of the injured eye. RESULTS: In 44 eyes, the CCT was successfully compared between the injured and contralateral eyes. In 30 of these eyes (70%), the CCT in the injured eye was significantly thinner than that in the contralateral eye (P < 0.01). In 33 eyes, the clinical course of the injured eyes was followed. The CCT was increased and decreased by >30 µm in 11 (33%) and 6 eyes (18%), respectively, and remained the same in 16 eyes (49%). The ratio of luminal and stromal areas in the choroid had significantly increased from 1.72 ± 0.54 at the initial visit to 1.87 ± 0.55 at the last visit (P < 0.001). In four eyes, a hemispherical dark space was observed beneath the sclerochoroidal interphase at the initial visit. CONCLUSION: The choroidal structure and its luminal and stromal properties are dynamically altered during the clinical course of commotio retinae.

Venous overload choroidopathy: A hypothetical framework for central serous chorioretinopathy and allied disorders.

In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals.