Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration.

PURPOSE: This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age-related macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. METHODS: We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups. RESULTS: Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (P < 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (P = 0.037) at 1 month than the IVF group, but there was no difference at 4 months (P = 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment. CONCLUSIONS: Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-naïve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.

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.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

IMPACT OF GAS/AIR TAMPONADE ON REFRACTIVE OUTCOMES AFTER FLANGED INTRASCLERAL INTRAOCULAR LENS FIXATION.

PURPOSE: This study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral intraocular lens (IOL) fixation combined with vitrectomy with or without gas/air tamponade. METHODS: The eyes were divided into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, and Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the Sander-Retzlaff-Kraff Theoretical formula. Then, the prediction error was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error was calculated as the absolute value of the prediction error for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, P < 0.0001, Group B, r = 0.943, P < 0.0001, linear regression analysis). The prediction error demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 diopter, Group B, -0.59 ± 0.95 diopter). There was no significant difference in prediction error and absolute prediction error between the two groups ( P = 0.44, P = 0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

Hyperreflective material in patients with non-neovascular pachychoroid disease.

BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. CONCLUSION: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Predicting retinal sensitivity using optical coherence tomography parameters in central serous chorioretinopathy.

PURPOSE: To predict changes in retinal sensitivity using optical coherence tomography (OCT) in eyes with central serous chorioretinopathy (CSC). METHODS: Twenty-three eyes in 23 patients with CSC were enrolled. Retinal sensitivity was measured twice using microperimetry in all the examined eyes. Spectral domain OCT measurements were simultaneously conducted. The relationship between retinal sensitivity and the thicknesses of (i) the retinal nerve fiber layer plus the ganglion cell layer (RNFL + GCL), (ii) the inner nuclear layer (INL), (iii) the outer nuclear layer (ONL), and (iv) the serous retinal detachment height (SRDH) were investigated in a point-wise manner. The associations between the change in retinal sensitivity and the OCT parameters at baseline were also investigated. RESULTS: The mean age of the participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p < 0.001), and the mean retinal sensitivity (p < 0.001) was significantly higher at the second examination, compared with the first; however, the logMAR visual acuity (VA) did not differ significantly between the two examinations (p = 0.063). The logMAR VA was associated with retinal sensitivity at both the first and second examinations (p < 0.001). The retinal sensitivity at the second examination was significantly correlated with the retinal sensitivity, RNFL + GCL, INL, ONL, and SRDH at the first examination and with the improvement in SRDH. CONCLUSIONS: Retinal sensitivity was associated with the retinal structure in eyes with CSC; these parameters could be useful for predicting the change in visual function prior to treatment.

Relationship between the vessel density around the optic nerve head and visual field deterioration in eyes with retinitis pigmentosa.

PURPOSE: To analyze the vessel density around the optic nerve head (ONH) by optical coherence tomography angiography (OCTA) in patients with retinitis pigmentosa (RP), and to evaluate its correlation with visual functions. METHODS: Thirty-eight eyes with RP with visual field constriction within the central 10° were enrolled. The mean (± SD) age of the patients was 43.7 ± 15.1 years. In addition to visual acuity (VA) measurements and visual field tests (Humphrey Field Analyzer 10-2 test), we also measured the vessel density at the macula by OCTA (superficial and deep vessel density: sVD(m) and dVD(m)) and in multiple layers around the ONH (vessel density in the radial peripapillary capillary [RPC] layer and in the nerve head [NH] layer: VDrpc and VDnh). The vessel density was calculated by binarizing the OCTA images. The associations between the logMAR VA and mean deviation (MD) values and the variables of central retinal thickness (CRT), sVD(m), dVD(m), VDrpc, VDnh, and also the size of the foveal avascular zone were investigated. RESULTS: The mean logMAR VA was 0.16 ± 0.34 and the MD value was - 17.2 ± 10.3 dB; the MD value was significantly related to the logMAR VA (p = 0.0028). Multivariate analysis with AICc model selection suggested only dVD(m) was associated with logMAR VA. On the other hand, the optimal model for the MD value included the CRT, dVD(m), and VDnh. CONCLUSION: The vessel density in the deep layer around the ONH was significantly associated with the visual field deterioration in patients with RP.

One-year outcome of combination therapy with intravitreal anti-vascular endothelial growth factor and photodynamic therapy in patients with pachychoroid neovasculopathy.

PURPOSE: To identify the functional outcome and evaluate the morphologic changes of patients with pachychoroid neovasculopathy (PNV) undergoing intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) at the 1-year follow-up. METHODS: We retrospectively studied all the treatment-naïve PNV patients who were scheduled to undergo combination therapy between September 2017 and November 2018. All the patients received three consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as loading doses. Full-dose PDT was performed within 1 week of the first injection. Retreatment was allowed if evidence of clinical deterioration or the presence of fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The best-corrected visual acuity (BCVA) was compared before treatment and at 3, 6, and 12 months after the initial treatment. Changes in the central foveal thickness (CFT), central choroidal thickness (CCT), and retreatment rate during the maintenance phase were also evaluated. RESULTS: Eleven eyes were enrolled in this study. Significantly, better BCVA was observed at 12 months than at baseline (P = 0.010). The mean CFT significantly decreased from 331 ± 93 to 237 ± 72 µm at 12 months (P < 0.001). The mean CCT also significantly decreased from 361 ± 74 to 310 ± 83 µm at 12 months (P < 0.001). The mean number of injections per eye was 3.9 ± 1.3 during the follow-up period. A total of 45.5% (5 /11) of the patients required retreatment during the maintenance phase. CONCLUSION: Anti-VEGF combined with full-dose PDT was well tolerated and appeared to be effective treatment for patients with treatment-naïve PNV. Combination therapy might also reduce the treatment burden with fewer injections in patients with PNV.

Optical coherence tomography characteristics of taxane-induced macular edema and other multimodal imaging findings.

PURPOSE: To identify common optical coherence tomography (OCT) characteristics of taxane-related CME (T-CME) to differentiate it from CME associated with other causes (O-CME) and to present multimodal imaging findings of T-CME. METHODS: To differentiate T-CME from O-CME, pooled SD-OCT images from 14 previous publications and images obtained from our multicenter case series of 3 patients with multimodal imaging of T-CME were compared with 16 consecutive cases of O-CME. Images were graded by 2 masked retinal specialists based on the presence of pre-specified OCT characteristics such as CME centered around fovea, outer retinal cysts more prominent compared with inner retinal cysts, continuous outer plexiform layer (OPL) and inner plexiform layer (IPL), intact outer retina layer, attenuation of outer retina layers by overlying retinal layers, and the presence of subretinal fluid. RESULTS: Comparing 19 and 16 SD-OCT images of T-CME and O-CME, respectively, T-CME showed a significantly higher rate of the continuous OPL and IPL layer and a higher composite score of the various pre-specified OCT features. All other individual features showed no significant difference between T-CME and O-CME. All our patients had T-CME that had vague petalloid patterns on the late-stage FFA, with late leakage on ICGA. OCT angiography in one case showed an intact foveal avascular zone. CONCLUSIONS: T-CME is a rare but important complication of taxane chemotherapy. Specific OCT features such as an intact continuous OPL and IPL layer combined with other OCT features can help distinguish T-CME from O-CME, and early diagnosis is clinically important as cessation of taxanes before the retinal layers are disrupted may prevent permanent vision loss.

Variable response of subretinal hyperreflective material to anti-vascular endothelial growth factor classified with optical coherence tomography angiography.

PURPOSE: To evaluate the prognosis and response of neovascular age-related macular degeneration (AMD) to anti-vascular endothelial growth factor (VEGF), according to the components of subretinal hyperreflective material (SHRM) classified using optical coherence tomography angiography (OCTA), is the aim of this study. METHODS: We retrospectively studied 39 eyes of 39 consecutive patients with SHRM associated with exudative AMD, who underwent standard examination and multimodal imaging, including fundus photography, optical coherence tomography (OCT), and OCTA. We classified SHRM into type 2 neovascularization (NV), fibrosis, subretinal hyperreflective exudation (SHE), and hemorrhage using OCTA. If compound SHRM was found, components in the foveal center were considered. All patients except one with fibrosis received anti-VEGF treatment for more than 12 months. The best-corrected visual acuity (BCVA) values measured before treatment and at 3, 6, and 12 months after the first injection were compared according to the components of SHRM. RESULTS: Using OCTA, 11 eyes with type 2 NV showed abnormal blood flow and 1 eye with fibrosis showed strong surface projection. Both SHE and hemorrhage components showed projection artifact with no intrinsic flow. However, OCTA enabled eyes with SHE (17 eyes) to be distinguished from those with hemorrhage (10 eyes) because hemorrhage showed masking of choriocapillaris flow. Eyes with SHE showed a significant improvement in the mean logMAR BCVA as compared with the value at the baseline, which was sustained throughout the 12-month follow-up period (p < 0.05). In eyes with type 2 NV and hemorrhage, no significant difference in the mean BCVA values was observed at any follow-up time-point (all, p > 0.05). CONCLUSION: OCTA was useful to noninvasively distinguish SHRM components. It may be important to consider the components of SHRM to predict the visual acuity in patients with AMD.

INTRAVITREAL INJECTION OF AFLIBERCEPT IN PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY: A 3-YEAR FOLLOW-UP.

PURPOSE: To compare the 3-year follow-up results of intravitreal injections of aflibercept between fixed dosing (FD) regimen and a pro re nata (PRN) regimen after three initial monthly doses for the treatment of polypoidal choroidal vasculopathy and to analyze factors influencing improvement in visual acuity. METHODS: We retrospectively studied all treatment-naive patients with polypoidal choroidal vasculopathy who were scheduled to receive intravitreal aflibercept injections FD or PRN after induction treatment between March 2013 and May 2014. Best-corrected visual acuity was evaluated before treatment and at 4, 12, 24, and 36 months after initial treatment. Factors that influence improvement in visual acuity were also investigated. RESULTS: Thirty-three eyes were assessed at the 3-year follow-up examination. Twenty-three eyes were treated with intravitreal aflibercept injections every 2 months for at least 1 year after three initial monthly doses (FD group), and 10 eyes were treated PRN after loading doses (PRN group). In the FD group, during the follow-up period from 1 to 3 years, quarterly dosing with capped PRN or a treat and extend regimen were selected. The mean number of administered intravitreal aflibercept was 15.3 ± 4.6 in the FD group and 9.0 ± 8.9 in the PRN group, with a significant difference between the two groups (P = 0.004). Significant improvement of the mean logarithm of the minimum angle of resolution values for best-corrected visual acuity was shown at 36 months, as compared to baseline values (P = 0.019). No significant difference in the improvement of best-corrected visual acuity between the two groups was observed at baseline or at 4, 12, 24, and 36 months after treatment (all P > 0.05), although there was a trend toward better results in the FD group. Multiple regression analysis showed that the FD group had better visual acuity at 36 months and greater improvement in visual acuity than the PRN group (P = 0.031 for both comparisons). CONCLUSION: Intravitreal aflibercept was effective in improving the vision of patients with polypoidal choroidal vasculopathy, as evaluated at the 3-year follow-up. Fixed treatment might be an important factor influencing improvement in visual acuity.

Flanged Intrascleral Intraocular Lens Fixation with Double-Needle Technique.

PURPOSE: To report the clinical outcomes of a new technique for transconjunctival intrascleral fixation of an intraocular lens (IOL). DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: One hundred eyes of 97 consecutive patients with aphakia, dislocated IOL, or subluxated crystalline lens who underwent posterior chamber sutureless implantation of an IOL were studied. METHODS: Two angled incisions parallel to the limbus were made by 30-gauge thin-wall needles. Haptics of an IOL were externalized with the needles and cauterized to make a flange of the haptics. The flange of the haptics were pushed back and fixed into the scleral tunnels. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA), corneal endothelial cell density, IOL tilt, and complications were determined. RESULTS: The IOLs were fixed with exact centration and axial stability. The mean preoperative best-corrected VA was 0.25 logarithm of the minimum angle of resolution (logMAR) units; after surgery, it improved significantly to 0.11 logMAR, 0.09 logMAR, 0.12 logMAR, and 0.04 logMAR at 6, 12, 24, and 36 months, respectively (P < 0.01, P < 0.01, P = 0.03, and P = 0.10, respectively). The mean corneal endothelial cell density decreased from 2341 cells/mm2 before surgery to 2313 cells/mm2, 2240 cells/mm2, 2189 cells/mm2, and 2244 cells/mm2 at 6, 12, 24, and 36 months, respectively (P < 0.01, P < 0.01, P < 0.01, and P = 0.17, respectively). The mean IOL tilt was 3.4°±2.5°. The postoperative complications included iris capture by the IOL in 8 eyes (8%), vitreous hemorrhage in 5 eyes (5%), and cystoid macular edema in 1 eye (1%). There were no incidents of postoperative retinal detachment, endophthalmitis, or IOL dislocation. CONCLUSIONS: We have developed a new technique for intrascleral IOL fixation. The flanged IOL fixation technique is a simple and minimally invasive method for achieving good IOL fixation with firm haptic fixation.

Visual outcomes of intraocular inflammation after brolucizumab injection in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: This study investigates the visual outcomes of neovascular age-related macular degeneration (nAMD) patients who developed intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr). METHODS: We studied 285 eyes of 279 cases diagnosed with nAMD and focused on 18 eyes (6.3%) of 17 cases which developed IOI after IVBr. IVBr was performed either on the initial treatment or for switching of other anti-vascular endothelial growth factor agents during January 2020 to December 2021. We evaluated clinical features and the course of treatment of a 6-month follow-up after IOI occurred. RESULTS: Of 17 cases, 9 cases were male, 8 cases were female. Baseline logarithm of the minimum angle of resolution(logMAR) best-corrected visual acuity (BCVA) was 0.36, BCVA before IOI occurred was 0.30, and BCVA when IOI occurred was 0.43. 16 eyes (88.9%) had symptoms such as visual loss or floaters when IOI occurred. On the other hand, the remaining 2 eyes (11.1%) had no symptoms. 11 eyes (61.1%) had only IOI, while the remaining 7 eyes (38.9%) had IOI and perivascular sheathing. Steroid sub-tenon injection was performed on 1 eye (5.6%), steroid eye drops were used in 11 eyes (61.1%), and 6 eyes (33.3%) were followed-up without treatment. Neovascular AMD recurred in 16 eyes (88.9%) after IOI occurred and were treated with aflibercept. VA at 3 and 6 months after IOI occurred were significantly improved to 0.34 and 0.30, respectively (P = 0.09 at 3 months and P = 0.02 at 6 months). The symptoms of patients were improved in all cases. We were able to stop steroid treatment in all cases. CONCLUSIONS: IOI occurred in 6.3% of nAMD patients after IVBr treatment. All of which showed significant improvement from logMAR of 0.43 to 0.30 with steroid treatment or without any treatment. We should consider the possibility of IOI after IVBr as a complication, however, they have a relatively good prognosis if treated at an early stage.

Peripapillary vessel density in eyes with cone-rod dystrophy.

PURPOSE: To compared the vessel density (VD) around the optic nerve head (ONH) in eyes with cone-rod dystrophy (CORD) and healthy control eyes in a sector-wise manner and to investigate the relationship between VD around the ONH and visual function in CORD eyes. METHODS: Twenty-six eyes in 14 CORD patients and 25 eyes in 25 healthy control subjects were examined. Using OCT angiography images, the VDs in the superficial and deep capillary plexus at the macula (sVDm and dVDm) and those around the ONH in the superior, temporal, inferior and nasal region (VDnh_s, VDnh_t, VDnh_i, and VDnh_n, respectively) were measured for each eye. Patient age, visual acuity (VA) and VDs were then compared between two groups. Moreover, the relationships between VA and the VDs were analyzed using a linear mixed model and AICc model selection. RESULTS: No significant difference in age was seen between the CORD and control groups (p = 0.87, Wilcoxon rank sum test), but the VA was significantly lower in the CORD group (p<0.0001). Both sVDm and dVDm were significantly lower in the CORD eyes than in the control eyes (both p<0.0001). Among VDnh_s, VDnh_t, VDnh_i, and VDnh_n, however, only VDnh_t differed significantly between the CORD and control groups (p = 0.035). Among age, VDnh_t, dVDm, and sVDm, the optimal model for VA included only VDnh_t and dVDm. CONCLUSIONS: In addition to the VD in the deep capillary plexus at the macula, the measurement of temporal VD around the ONH might be useful for predicting visual function in eyes with CORD.

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.

Intravitreal anti-vascular endothelial growth factor monotherapy in age-related macular degeneration with submacular hemorrhage.

The purpose of this study was to evaluate the 1-year visual outcomes of patients treated with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD). We retrospectively studied 62 treatment-naïve eyes with SMHs exceeding one disc area (DA) secondary to AMD treated with IVA or IVBr. All patients received three monthly intravitreal injections in the loading phase followed by as-needed injections or fixed dosing. If a vitreous hemorrhage (VH) developed during the follow-up period, injections were discontinued and vitrectomy was performed. We evaluated the changes in the best-corrected visual acuity (BCVA) and factors that affected the BCVA improvement and VH development. A VH during treatment developed in five eyes (8.1%) (VH + group), and the mean BCVA worsened from 0.45 to 0.92. The BCVA improved significantly (P = 0.040) in the remaining 57 eyes (VH - group) from 0.42 to 0.36. The development of VHs was associated with significantly (P < 0.001) less VA improvement. Furthermore, large DAs and younger age at baseline were associated significantly (P = 0.010 and 0.046, respectively) with the development of VHs. Both IVA and IVBr appeared to improve functional outcomes in patients with SMH secondary to AMD when VHs did not develop. However, a VH developed in 8.1% of eyes after treatment. Although anti-vascular endothelial growth factor treatments were well-tolerated, for cases with large SMH at baseline, it should be considered that VH may occur during the monotherapy treatment process using IVA or IVBr, and that achieving good visual outcomes may be difficult in some cases.

Retinal Morphologic Features in Patients with Large Macular Holes Treated by Autologous Neurosensory Retinal Transplantation.

PURPOSE: To investigate the time courses of morphologic changes in the transplanted grafts, including the retinal layer, the ellipsoid zone (EZ) and the visual acuity (VA) after autologous retinal transplantation (ART) in patients with primary large macular holes (MHs). DESIGN: Single-center, retrospective cohort study. SUBJECTS: The study included 17 eyes of 17 patients who had undergone ART. All patients fulfilled the following criteria: (1) MH was the only disease-causing anatomic abnormality of the macula; (2) they could be followed up for at least 12 months after ART surgery; (3) they had no other systemic disorders; and (4) the MH was > 400 µm in diameter. METHODS: Data of all patients who underwent assessment of the VA and spectral-domain (SD)-OCT at 1, 3, 6, and 12 months after surgery were analyzed. The morphologic features of the graft and the EZ were measured by SD-OCT. MAIN OUTCOME MEASURES: Changes in the morphologic features of the graft (graft thickness, overall graft area, graft length, area of outer retina, and EZ) and VA over 1 year after surgery. RESULTS: Closure of the MH was achieved in all patients. The VA was 0.59 ± 0.27 (logarithm of the minimal angle of resolution units) at 1-year postsurgery compared with 0.84 ± 0.22 before surgery (P < 0.05). The retinal layers gradually became smoothly connected. Although a decrease in graft thickness and overall graft area was observed, the length and area of the outer retina were maintained throughout the follow-up period. The presence of the EZ was observed in 9 patients (52.9%) and our analyses revealed significantly greater improvement of VA in these patients than in those without the EZ (P < 0.05). Moreover, the incidence of macular edema (ME) was higher in the group without the EZ (P = 0.04; chi-square test). CONCLUSION: Patients showed significant improvements of the VA. Morphologically, the layers were gradually connected to each other, and the outer retina was particularly maintained. Especially, patients in whom an EZ was restored in the graft showed a low prevalence of ME and greater improvement of the VA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.