Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy.

PURPOSE: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months. RESULTS: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R2 = 0.171, P = 0.056) and a greater displacement of SMH (R2 = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001). CONCLUSIONS: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

Association of disorganization of retinal inner layers with optical coherence tomography angiography features in branch retinal vein occlusion.

PURPOSE: To examine the associations between the disorganization of the retinal inner layers (DRIL) and optical coherence tomography angiography characteristics and visual acuity (VA) outcomes in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: In this single-center cross-sectional cohort study, the data of 43 patients with macular edema secondary to BRVO that received pro re nata anti-vascular endothelial growth factor therapy were analyzed. B-scan and en face angiographic images were obtained by swept-source-based wide-field optical coherence tomography angiography performed at a single visit 1 month after the anti-vascular endothelial growth factor therapy session and evaluated. Correlations between the vascular indices in macula-centered 3 × 3 and 12 × 12 mm2 areas and B-scan parameters, such as DRIL length and VA, were examined. RESULTS: The mean DRIL length (Rs = 0.588, p < 0.001) and the proportion of scans with DRIL out of five scans (Rs = 0.507, p = 0.001) were significantly correlated with the final best-corrected VA in patients with BRVO. DRIL length was associated with vascular density (VD) and vascular length in the macula (Rs = - 0.425, p = 0.006 and Rs = - 0.382, p = 0.013, respectively), but not with VD and vascular length in the larger areas (12 × 12 mm2). Multilinear regression analysis revealed that the extent of macular edema (p = 0.0016) and VD in the 3 × 3 mm2 area (p = 0.004) was significantly associated with the DRIL development. CONCLUSION: DRIL severity was correlated with VA and associated with the peri-macular perfusion status in eyes with BRVO. Macular edema and macular perfusion affected DRIL severity. These findings would help understand the pathogenesis of DRIL in eyes with BRVO.

Long-term outcomes of intravitreal activated protein C injection for ischemic central retinal vein occlusion: an extension trial.

PURPOSE: Our previous 1-year pilot study evaluated the efficacy of intravitreally injected activated protein C (APC) in 10 eyes with ischemic central retinal vein occlusion (CRVO). The reperfusion of the areas of retinal nonperfusion (RNP) exceeded 50% of the baseline in five (50%) eyes 1 year after the APC injection. The current study evaluated the long-term efficacy and safety of intravitreal APC. METHODS: The 10 eyes in the pilot study were included in this study. Other treatments were administered at the physicians' discretion after the pilot study. We evaluated visual acuity (VA), central retinal thickness (CRT) and perfusion status, and adverse events and severity over the long term. RESULTS: The median follow-up was 60 months (range, 48-68 months). Compared with baseline, the post-treatment VA improved significantly (P < 0.001) from 1.39 to 1.06 logarithm of the minimum angle of resolution. The CRT improved significantly (P < 0.001) from 1090 to 195 µm at the last visit. The RNP areas decreased from an average 29.7 disc areas (DAs) at baseline to an average 16.5 DAs at the last examination (mean, 40 ± 6.5 months after the first APC treatment). No adverse events were related to intravitreal APC. CONCLUSION: No complications were associated with intravitreal APC, the clinical course improved, and improved RNP was maintained for the long term, suggesting that intravitreal APC may be an alternative treatment for CRVO.

Flow pattern and perforating vessels in three different phases of myopic choroidal neovascularization seen by swept-source optical coherence tomography angiography.

PURPOSE: To compare the choroidal neovascularization (CNV) flow patterns and the relationship between perforating vessels (PVs) and CNV in the three different stages of networks in myopic CNV (mCNV) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This retrospective study included 28 eyes with mCNV that was divided into three phases (active, scar, and atrophic) and observed by SS-OCTA. SS-OCTA findings, with special focus on the relationship between the PVs and CNV, were compared among the three phases. RESULTS: Overall, the CNV signal was detected in 31 of the 34 areas of CNV (91%); in the active, scar, and atrophic phases, respectively, CNV signals were detected in eight of eight areas of CNV (100%), 10 of 11 areas of CNV (91%), and 13 of 15 areas of CNV (86%). Two signal patterns were observed in each phase, i.e., dense and loop; in the atrophic phase, seven eyes were unclassifiable. The ratio between the dense and loop patterns did not differ significantly among the phases. In 30 of 34 areas of CNV for which clear images were obtained, the PVs and CNV were connected directly or indirectly in 19 area of CNV, and in five areas of CNV, trunk-like vessels were connected to the PVs within the CNV. The numbers of foveal or parafoveal CNVs accompanied by PVs were significantly (p=0.0048) greater than those of the extrafoveal CNV. CONCLUSIONS: OCTA provides detailed observation of mCNV and the relationship between CNV and PVs. Although the CNV signal pattern does not differ depending on the degree of atrophy, there are cases in which only the trunk-like vessels connect to the PVs within the CNV in the atrophic phase without CNV flow signal.

Impact of photoreceptor density in a 3D simulation of panretinal laser photocoagulation.

BACKGROUND: During panretinal photocoagulation (PRP), the outer retina, especially the photoreceptors, are destroyed. During such procedures, the impact of the retinal photocoagulation, which is performed in the same photocoagulated area, may change if it is applied to different locations with different photoreceptor densities. Thus, we aimed to evaluate the influence of photoreceptor density on PRP. METHODS: We constructed a three-dimensional (3D) average distribution of photoreceptors with 3D computer-aided design (CAD) software using previously derived photoreceptor density data and calculated the number of photoreceptors destroyed by scatter PRP and full-scatter PRP (size 400-µm on the retina, spacing 1.0 spot) using a geometry-based simulation. To investigate the impact of photoreceptor density on PRP, we calculated the ratio of the number of photoreceptors destroyed to the total number of photoreceptors, termed the photoreceptor destruction index. RESULTS: In this 3D simulation, the total number of photoreceptors was 96,571,900. The total number of photoreceptors destroyed by scatter PRP and full-scatter PRP were 15,608,200 and 19,120,600, respectively, and the respective photoreceptor destruction indexes were 16.2 and 19.8%, respectively. CONCLUSIONS: Scatter PRP is expected to have 4/5 of the number of photoreceptors destroyed by full-scatter PRP.

Tachyphylaxis during treatment of exudative age-related macular degeneration with aflibercept.

PURPOSE: At present, the standard treatment of neovascular age-related macular degeneration (AMD) is the repeated administration of antivascular endothelial growth factor (VEGF) agents. However, we often encounter patients who develop tachyphylaxis for anti-VEGF agents. In this study, we investigated the characteristics of patients who developed tachyphylaxis on repeated intravitreal aflibercept (IVA) injections for neovascular AMD and the frequency of tachyphylaxis. METHODS: Three hundred thirteen eyes (313 patients) with treatment-naïve AMD who achieved resolution soon after starting IVA and were followed up for ≥ 12 months were enrolled in this retrospective, interventional, consecutive case series. The eyes were investigated for tachyphylaxis to aflibercept. Tachyphylaxis was defined as absence of any improvement (more than 100 µm) in or worsening of CRT within 1 month after more than two repeated monthly IVA injections when the exudative change remained. RESULTS: Twenty-eight (8.9%) of the 313 eyes developed tachyphylaxis (occult with no classic, n = 14; polypoidal choroidal vasculopathy, n = 14) at an annual rate of about 3%. The mean number of IVA injections was 10.5 ± 7.8, and the mean interval until tachyphylaxis was 20.9 ± 14.0 months. There was a significant difference in the AMD subtypes between the group with tachyphylaxis and the group without it (p = 0.0029). Occult with no classic type and polypoidal choroidal vasculopathy were the only AMD subtypes in the eyes with tachyphylaxis. In the analysis of the eyes that had occult with no classic or polypoidal choroidal vasculopathy, only intraretinal edema was significantly less common (p = 0.042). A combination of photodynamic therapy and aflibercept was effective in 13 (87%) of 15 eyes with tachyphylaxis, and switching to intravitreal ranibizumab was effective in 5 (56%) of 9 eyes. CONCLUSIONS: Tachyphylaxis occurs after repeated IVA injections in a minority of patients with AMD for a long term and is more likely to occur in eyes with lesions beneath the retinal pigment epithelium and no intraretinal edema. Treatment of AMD should be performed keeping this fact in mind, while considering the consecutive treatment.

Effect of intravitreal injection of aflibercept or ranibizumab on chorioretinal atrophy in myopic choroidal neovascularization.

PURPOSE: To compare chorioretinal atrophy (CRA) progression in myopic choroidal neovascularization (mCNV) between intravitreal injections of ranibizumab (IVR) and aflibercept (IVA) in the eyes with mCNV. METHODS: Thirty eyes (28 patients) with treatment-naïve mCNV were included in this study. IVR or IVA was administered for up to 1 year. The best-corrected visual acuity (BCVA) was measured, and fundus photographs and fundus autofluorescence were obtained before and 1, 3, 6, and 12 months after the initial treatment. The clinical characteristics including the macular choroidal thickness in various areas and CRA progression were compared between the drugs. The clinical characteristics and macular choroidal thicknesses were compared between eyes with and without CRA progression. RESULTS: The BCVA improved significantly (p < 0.05 for all comparisons) from 0.44 to 0.26, 0.19, 0.20, and 0.17 after 1, 3, 6, and 12 months, respectively. CRA progressed in 12 (40%) eyes over 1 year. The CRA progression did not differ significantly between aflibercept and ranibizumab. The foveal choroid was significantly (p = 0.0043) thinner in aflibercept-treated eyes compared with ranibizumab-treated eyes at 1 year. Subfoveal CNV tended to cause CRA progression more frequently at 1 year, although this did not reach significance. CONCLUSIONS: IVA to treat mCNV caused more severe thinning of the foveal choroid than ranibizumab; however, no significant difference was seen in CRA progression between the drugs and the choroidal thickness should not be associated with CRA progression. The CNV location may predict CRA progression after anti-vascular endothelial growth factor therapy for mCNV.

A Multicenter Randomized Controlled Study of Antioxidant Supplementation with Lutein for Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. PROCEDURES: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. RESULTS: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). CONCLUSIONS: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies.

Modification of Dentofacial Growth Associated with Goldenhar Syndrome.

The rare developmental defect, Goldenhar syndrome is characterized by complex craniofacial and dentofacial anomalies. Here we describe the successful orthodontic treatment of a 5-year-old Japanese Goldenhar syndrome patient with mild facial asymmetry, right microtia, right-side hearing loss, and tongue-thrusting by a modification of dentofacial growth using a non-surgical orthopedic treatment approach. Improvement of the vertical discrepancies on the affected side and canted occlusal plane as well as mandibular deviation were achieved with a functional orthopaedic approach. Stable and acceptable occlusion were obtained over the 32-month post-retention period. A non-surgical orthodontic treatment approach offers satisfactory facial aesthetic outcomes in Goldenhar syndrome.

ONE-YEAR RESULTS OF INTRAVITREAL AFLIBERCEPT FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate the 1-year results of intravitreal aflibercept injections for polypoidal choroidal vasculopathy based on indocyanine green angiography findings. METHODS: Twenty-nine eyes with treatment-naive polypoidal choroidal vasculopathy treated with intravitreal aflibercept injections and followed longer than 1 year were retrospectively reviewed. The best-corrected visual acuity, optical coherence tomography findings, and polypoidal lesions in indocyanine green angiography were evaluated. RESULTS: The mean number of injections through 1 year was 3.9 ± 1.9 (range: 1-8). Fourteen eyes (48%) were received no additional injections because of no recurrence of exudative change after the first loading dose. The mean best-corrected visual acuity levels at 6 months and 1 year significantly improved, and the mean central retinal thickness significantly decreased at all observation points from the baseline. At 3 months, the polypoidal lesions completely resolved in 19 (66%) eyes. At 1 year, the complete resolution of polypoidal lesions was seen in 4 of 10 eyes with persistent polypoidal lesions at 3 months. However, polypoidal lesions recurred at 1 year in 5 of 19 eyes (26%) with complete resolution of polypoidal lesions at 3 months. CONCLUSION: Aflibercept is effective for the eyes with treatment-naive polypoidal choroidal vasculopathy to achieve the resolution of polypoidal lesions. The authors need to carefully observe the eyes after confirming complete resolution of polypoidal lesion because of recurrent polyps seen in one-quarter of the study eyes.

Involvement of multiple CCN family members in platelets that support regeneration of joint tissues.

OBJECTIVES: Platelet-rich plasma (PRP) has been widely used to enhance the regeneration of damaged joint tissues, such as osteoarthritic and rheumatoid arthritic cartilage. The aim of this study is to clarify the involvement of all of the CCN family proteins that are crucially associated with joint tissue regeneration. METHODS: Cyr61-CTGF-NOV (CCN) family proteins in human platelets and megakaryocytic cells were comprehensively analyzed by Western blotting analysis. Production of CCN family proteins in megakaryocytes in vivo was confirmed by immunofluorescence analysis of mouse bone marrow cells. Effects of CCN family proteins found in platelets on chondrocytes were evaluated by using human chondrocytic HCS-2/8 cells. RESULTS: Inclusion of CCN2, a mesenchymal tissue regenerator, was confirmed. Of note, CCN3, which counteracts CCN2, was newly found to be encapsulated in platelets. Interestingly, these two family members were not detectable in megakaryocytic cells, but their external origins were suggested. Furthermore, we found for the first time CCN5 and CCN1 that inhibits ADAMTS4 in both platelets and megakaryocytes. Finally, application of a CCN family cocktail mimicking platelets onto HCS-2/8 cells enhanced their chondrocytic phenotype. CONCLUSIONS: Multiple inclusion of CCN1, 2 and 3 in platelets was clarified, which supports the harmonized regenerative potential of PRP in joint therapeutics.

Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins.

Cilia and flagella are highly conserved organelles that have diverse roles in cell motility and sensing extracellular signals. Motility defects in cilia and flagella often result in primary ciliary dyskinesia. However, the mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are only poorly understood. Here we report a new gene, kintoun (ktu), involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families as well as in the pf13 mutant of Chlamydomonas. In the absence of Ktu/PF13, both outer and inner dynein arms are missing or defective in the axoneme, leading to a loss of motility. Biochemical and immunohistochemical studies show that Ktu/PF13 is one of the long-sought proteins involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment.

Characteristics of central serous chorioretinopathy complicated by focal choroidal excavation.

PURPOSE: To investigate the characteristics of central serous chorioretinopathy complicated by focal choroidal excavation (FCE) using fundus angiography and optical coherence tomography (OCT). METHODS: A retrospective single-institution study. We reviewed the charts of 7 eyes of 7 patients (5 men, 2 women; mean age, 56.9 ± 9.8 years) with central serous chorioretinopathy complicated by FCE using fundus angiography and OCT. RESULTS: In six of the seven eyes, the points of leakage were at the edge of FCE on OCT. All FCE lesions were hypofluorescent from early to late phase on indocyanine green angiography. All eyes had late-phase hyperfluorescence on indocyanine green angiography secondary to choroidal vascular hyperpermeability around the FCE lesion. Five fellow eyes also had choroidal vascular hyperpermeability. The mean subfoveal choroidal thicknesses by swept source high-penetration OCT were 377 µm and 333 µm in the fellow eyes, a difference that did not reach significance (P = 0.21). CONCLUSION: Fundus angiography and OCT showed that choroidal circulatory disruption and atrophic retinal pigment epithelium at the FCE lesion might be related to central serous chorioretinopathy complicated by FCE.

Effect of polyp regression and reduction on treatment efficacy in polypoidal choroidal vasculopathy treated with aflibercept.

Intravitreal injection of aflibercept (IVA) has successfully treated polypoidal choroidal vasculopathy (PCV), and polyp morphology is an important indicator of treatment efficacy. However, many studies have not reported the presence or absence of polyp regression and treatment outcomes, and few studies have reported polyp reduction and treatment outcomes in cases with residual polyps. We retrospectively measured the polyp area on indocyanine green angiography images before and after the IVA loading phase and investigated the regression and reduction of polyps and treatment outcomes of 81 eyes with PCV treated with IVA. We investigated the relationship between the presence or absence of complete regression of polyps and the percentage change in the polyp area and treatment outcomes. Eyes with complete polyp regression had significantly better visual acuity improvements compared with baseline at 12 months (P = 0.0108), fewer treatments (P = 0.0024), fewer recurrences during 12-months follow-up (P = 0.0010), and more "dry maculas" at 3 months (P = 0.0048) than eyes in which polyp regression did not occur. A significant correlation was seen only between the percentage of polyp regression and visual acuity at 3 months (P = 0.0395). Regarding IVA therapy for PCV, the presence or absence of complete polyp regression at the end of the loading phase affected the treatment outcome, whereas the degree of polyp reduction in cases of residual polyps had no effect.

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

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

Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy.

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 µm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2;P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Refractory Age-Related Macular Degeneration Due to Concurrent Central Serous Chorioretinopathy in Previously Well-Controlled Eyes.

Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond to repeated intravitreal aflibercept. Fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography revealed focal leakage spots, choroidal hyperpermeability, and dilated choroidal vessels, respectively, which were distinct from the pre-existing choroidal neovascularization and suggestive of newly developed CSCR. Laser photocoagulation of the leak spots resulted in the complete resolution of the once-refractory subretinal fluid and the maintenance of vision. Conclusions: Our cases highlight that anti-VEGF-refractory subretinal fluid may occur secondary to concurrent CSCR in patients receiving regular anti-VEGF treatments for AMD. In those patients, treatment for CSCR is effective for controlling subretinal fluid that is unresolved by anti-VEGF treatment.

Three cases of macular retinal detachment exacerbated during follow-up with myopic foveoschisis around myopic choroidal neovascularization.

Purpose: Myopic choroidal neovascularization (CNV) and myopic traction maculopathy are major complications of pathologic myopia, and myopic foveoschisis (MF) is one of several symptoms that can be included under the general term "myopic traction maculopathy"; however, only a few cases will have MF around the myopic CNV. We report three cases with MF around myopic CNV that followed different clinical courses observed using swept-source optical coherence tomography. Observations: Case 1 was a 69-year-old woman with an axial length of 29.71 mm, myopic CNV, and MF in the left eye. One month after intravitreal injection of ranibizumab (IVR), a macular retinal detachment (RD) expanded. Vitrectomy and gas tamponade were performed during month 2; the macular RD and MF resolved gradually thereafter. Case 2 was a 54-year-old man with an axial length of 30.59 mm, myopic CNV, and MF in the right eye; after IVR, a macular RD developed and gradually expanded until month 4; the RD and MF resolved spontaneously and resolved during month 8. Case 3 was a 66-year-old woman with an axial length of 28.63 mm, myopic CNV, and MF in the left eye. A macular RD expanded 1 month after a previous vitrectomy for MF; after intravitreal injection of aflibercept, the macular RD and MF resolved gradually in month 12. In all cases, the CNV was accompanied by subretinal fluid, and two of the three cases had outer lamellar holes. Conclusion and Importance: The MF around the myopic CNV may lead to exacerbated MF and RD during follow-up, and the subretinal fluid caused by the CNV might facilitate MF progression. Since this condition is rare, further investigation of this entity is needed to determine appropriate management.