Retinal arterial and vein occlusion: is surgery ever indicated?

PURPOSE OF REVIEW: To highlight the recent progression in surgical treatments for central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO). RECENT FINDINGS: Anti-VEGF treatment, accepted as a primary treatment for CRVO, is unable to effectively treat all types of the diseases. Regarding CRAO, there are not any accepted therapies available. There have however been recent innovations in surgery, such as utilizing robotics-assisted tools in cannulation procedures for central retinal artery occlusion, or micro-cystotomy for refractory macular edema resulting from ischemic CRVO. SUMMARY: Refractory macular edema due to CRVO can be treated with aspiration of the fluid found inside the large cysts often seen in edema. The success rate of micro-cystotomy has been reported at 78% in eyes with refractory macular edema. Recent studies have shown that cannulation with tissue plasminogen activator (tPA) is effective for eyes with CRAO due to thrombus.Recent cannulation or micro-cystotomy procedures can be enhanced with the use of robotic tools which allow us to perform this difficult procedure more easily. Newly developed technology, and consequent developments in surgical procedures, will allow us to deal with unmet needs for retinal vessel occlusive diseases.

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.

ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY IN DETERMINATION OF ENTRY SITE FOR VITRECTOMY IN HIGHLY MYOPIC EYES.

PURPOSE: To evaluate the efficacy of anterior segment optical coherent tomography (AS OCT) in estimating the length of the pars plana and optimizing the sclerotomy entry site in vitrectomy for highly myopic eyes, facilitating membrane peeling. METHODS: Twenty-three eyes with myopic traction maculopathy were studied. The pars plana was examined using two methods: preoperative AS OCT and intraoperative measurement. The distance from the limbus to the ora serrata in two groups was measured to compare differences in length. The actual length of the entry site from the limbus and forceps used were noted in all eyes studied. RESULTS: The mean axial length was 29.2 ± 2.3 mm for all 23 eyes. The average length between the limbus and ora serrata measured with AS OCT and intraoperative examination was 6,710 µ m (SD ± 459) and 6,671 µ m (SD ± 402), respectively, in the superotemporal region ( P > 0.05), and 6,340 µ m (SD ± 321) and 6,204 µ m (SD ± 402), respectively, in the superonasal region ( P >0.05). The mean length of the entry site from the limbus was 6.2 mm, and 28-mm forceps were used in 17 of 23 eyes (77%). CONCLUSION: The length of the pars plana varies depending on the axial length of the eye. Preoperative AS OCT enables accurate measurement of the pars plana in eyes with high myopia. AS OCT examination can help determine the optimal site for sclerotomy, allowing easier access to the macular region for membrane peeling in highly myopic eyes.

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.

Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases.

PURPOSE: The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID). METHODS: We retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID. RESULTS: The 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival. CONCLUSIONS: RIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID.

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.

AUTOLOGOUS RETINAL TRANSPLANTATION AS A PRIMARY TREATMENT FOR LARGE CHRONIC MACULAR HOLES.

PURPOSE: To report the outcomes of autologous neurosensory retinal transplant as a primary treatment for patients with large chronic macular holes and evaluate the safety and feasibility of the procedure. DESIGN: Retrospective study, consecutive case series. METHODS: We reviewed seven patients with a primary chronic large macular hole, who underwent autologous neurosensory retinal transplant. Mean preoperative minimum and maximum hole diameters were 643 µm and 1214 µm, respectively. Changes in visual acuity were measured postsurgery, and optical coherence tomography, fluorescein angiography, and microperimetry-3 were analyzed after the procedure. RESULTS: Closure of the macular hole was achieved in all seven eyes in the study. At 1 year post-surgery, there was significant improvement in mean visual acuity (LogMAR 1.10 vs. 0.68, P = 0.001). Optical coherence tomography showed that all grafts had formed attachments to the retinal epithelial cells of the recipient retina. Mean preoperative ellipsoid zone defect was 1,089 ± 403.8 µm (range, 918-1,329 µm) which further decreased to 921 ± 129.1 µm (range, 670-1,201 µm) at final follow up (P = 0.09). Microperimetry-3 testing indicated retinal sensitivity in the graft in five eyes. CONCLUSION: Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.

Low-frequency coding variants in CETP and CFB are associated with susceptibility of exudative age-related macular degeneration in the Japanese population.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method. We used a total of 2,886 (1st: 827, 2nd: 2,059) exudative AMD cases including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation and 9,337 (1st: 3,247 2nd: 6,090) controls. Gene-based analysis found a significant association of low-frequency variants (minor allele frequency (MAF) < 0.05) in CETP, C2 and CFB. The association of CETP remained after conditioned with all known genome-wide association study (GWAS) associated variants. In addition, when we included only disruptive variants, enrichment of rare variants (MAF < 0.01) was also observed after conditioned with all GWAS associated variants (P = 1.03 × 10−6, odds ratio (OR) = 2.48). Haplotype and conditional analysis of the C2-CFB-SKIV2L locus showed a low-frequency variant (R74H) in CFB would be individually associated with AMD susceptibility independent of the GWAS associated SNP. These findings highlight the importance of target sequencing to reveal the impact of rare or low-frequency coding variants on disease susceptibility in different ethnic populations.

Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

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.

One-year efficacy of adjunctive use of Ripasudil, a rho-kinase inhibitor, in patients with glaucoma inadequately controlled with maximum medical therapy.

PURPOSE: The aim of this study was to evaluate the one-year efficacy, ability to lower intraocular pressure, and tolerability of ripasudil, a rho-kinase inhibitor, in patients with glaucoma inadequately controlled with maximum medical therapy. METHODS: This prospective, non-comparative, interventional case-series study included 39 patients with primary open-angle glaucoma inadequately controlled with maximum medical therapy before treatment with ripasudil. Ripasudil was administered twice per day as adjunctive therapy to ongoing glaucoma treatment. The primary endpoint was the degree of intraocular pressure reduction after 12 months of treatment; the secondary endpoints were the incidence of adverse events. RESULTS: We examined 39 eyes. The intraocular pressure reduction (given as the relative percentage of intraocular pressure reduction) from baseline was -2.6 mmHg (-15.5%; 95% confidence interval, -1.1 to -3.9 mmHg; P < 0.001) after 12 months of treatment. The adverse events were conjunctival hyperemia (all patients), blepharitis (three), allergic conjunctivitis (two), punctate keratitis (two), and ophthalmalgia (one). CONCLUSIONS: Treatment with ripasudil decreased intraocular pressure in patients with glaucoma that was poorly controlled with maximal medical therapy, and it was well-tolerated.