Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

Long-Term Prognosis of Patients with Polypoidal Choroidal Vasculopathy Treated with Photodynamic Therapy.

We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), anatomical findings (vision-threatening findings), and treatment history were assessed. In total, 38 eyes underwent PDT as the initial treatment (initial PDT group) and 22 eyes underwent PDT as a rescue treatment (rescue PDT group). In the initial PDT group, 11 eyes (29%) did not require additional therapy throughout the observation period and maintained good BCVA. A total of 27 eyes (71%) underwent additional treatments and the mean BCVA was only stabilized for 2 years; thereafter, decreased vision occurred even with additional treatments. In the rescue PDT group, 22 eyes (95%) required additional treatment. Hard exudate, serous pigment epithelial detachment, and the total vision-threatening score were related to worse BCVA. Initial PDT may be effective in about 30% of cases with preservation of good vision and no need for additional treatment. However, patients with received rescue PDT needed additional treatment in most cases and the vision decreased in many cases.

The Role of Laser Photocoagulation in Treating Diabetic Macular Edema in the Era of Intravitreal Drug Administration: A Descriptive Review.

Background and Objectives: This study aimed to elucidate the role of laser photocoagulation therapy in the treatment of diabetic macular edema (DME) as an alternative to, or in conjunction with, the first-line treatment, anti-vascular endothelial growth factor (VEGF). Materials and Methods: A comprehensive literature search to identify studies that evaluated the efficacy of laser photocoagulation therapy in the management of DME was performed. The relevant findings of the efficacy of focal/grid laser therapy from data in randomized, controlled trials were synthesized, and the potential of new laser technologies, such as navigated laser systems, pattern scan lasers, and subthreshold lasers, was explored. The usefulness of multimodal imaging-guided laser therapy was also evaluated, with a focus on the potential contribution to anti-VEGF therapy. Results: Focal laser photocoagulation targeting microaneurysms remains an effective therapeutic approach to chronic refractory edema, despite the widespread use of anti-VEGF therapy. To achieve the best possible treatment outcomes, precise identification of microaneurysms is essential. This requires the use of multimodal imaging-guided, highly accurate, minimally invasive coagulation techniques. Subthreshold laser therapy can also reduce the frequency of anti-VEGF injections and minimize treatment burden. Conclusions: Further studies are needed to determine the optimal timing and settings for laser photocoagulation therapy and the potential of new laser technologies in the management of DME. Nevertheless, laser photocoagulation therapy plays an important role in the management of DME, in conjunction with anti-VEGF therapy.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

AUTOLOGOUS POSTERIOR CAPSULE FLAP TRANSPLANTATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE IN A PSEUDOPHAKIC EYE.

PURPOSE: To report a case of refractory macular hole (MH) in pseudophakic eye treated with autologous posterior capsule flaps transplantation. METHODS: Case report. RESULTS: A 48-year-old man visited our hospital with visual loss in the right eye because of unclosed MH. The patient had undergone two previous surgeries in another hospital, that is, the first included a cataract surgery, vitrectomy, and internal limiting membrane peeling with sulfur hexafluoride (SF 6 ) gas tamponade, and the second included an ineffective autologous internal limiting membrane flap technique and massaging the edges of the MH with a soft-tipped flute needle followed by the same gas, but the MH remained open. In our hospital, posterior capsule flaps were acquired from the same eye, inserted into the MH, and the same gas tamponade was performed, which was about four months after the disease onset (3 months after the prior second surgery). The patient kept face-down position for a week after the surgery and the MH was closed, which remained for over 12 months. The visual acuity improved from 20/250 to 20/60, and the retinal sensitivities around the MH gradually improved. CONCLUSION: An autologous posterior capsule flaps transplantation was effective in the management of refractory MH to not only close the MH but also improve the visual outcomes.

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.

Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: A multicenter survey from the Japan Clinical Retina Study (J-CREST) group.

PURPOSE: To evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM). METHODS: This retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed. RESULTS: Major causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001). CONCLUSIONS: The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

Visual prognosis of submacular hemorrhage secondary to age-related macular degeneration: A retrospective multicenter survey.

PURPOSE: To investigate the clinical features, treatment options, and visual outcomes of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). DESIGN: A retrospective, observational case series. METHODS: Setting: Multicenter institutional setting. Patient Population: A total of 127 patients (127 eyes; 88 men, 39 women; (mean age, 74.2 years)) diagnosed with AMD-associated SMHs exceeding 2 disc diameters involving the fovea. Observation: The AMD types, previous treatments, treatment options, anatomic findings, and best-corrected visual acuity (BCVA) were assessed. Main Outcome Measures: Clinical features, treatment options, and visual outcomes of SMHs secondary to nAMD. RESULTS: Thirty-two eyes had typical AMD, 94 eyes polypoidal choroidal vasculopathy (PCV), and one eye retinal angiomatous proliferation. Eighty-five eyes were treatment-naïve; 42 eyes were treated previously: anti-vascular endothelial growth factor (VEGF) therapy (n = 26), photodynamic therapy (n = 3), and combined therapy (n = 13). Treatment of SMHs included vitrectomy (36 eyes), pneumatic displacement (49 eyes), and anti-VEGF monotherapy (42 eyes). The final BCVA improved significantly in treatment-naïve cases from 0.86 to 0.62 logarithm of the minimal angle of resolution (logMAR) unit (Snellen equivalent from 20/145 to 20/83) and from 0.80 to 0.56 (Snellen equivalent from 20/126 to 20/73) in PCV cases. Meanwhile, the BCVA logMAR values improved from 1.15 to 0.75 (Snellen equivalent from 20/283 to 20/112) and from 0.87 to 0.63 (Snellen equivalent from 20/148 to 20/85) in eyes that underwent vitrectomy or pneumatic displacement, respectively. In eyes with BCVAs between 20/133 to 20/40 at SMH onset, the final VA in the pneumatic displacement group was better than in the anti-VEGF monotherapy group. One eye had a retinal detachment and 1 eye had a macular hole in the vitrectomy group, and 5 eyes had a vitreous hemorrhage in the pneumatic displacement group. CONCLUSIONS: The recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.

Multimodal Imaging of Subfoveal Pachydrusen Containing a Blood Flow Signal.

Individuals with pachydrusen, larger than 125 µm, have a significantly thicker choroid than do those with soft drusen or reticular pseudodrusen. Little is known about cases of abnormal blood flow within pachydrusen. The purpose of this report was to demonstrate a blood flow signal within pachydrusen using optical coherence tomography (OCT) angiography. A 76-year-old Japanese woman presented with innumerable drusen/pachydrusen in both posterior poles. Her visual acuity was good. OCT showed subfoveal pachydrusen in the left eye, but no exudative changes. The subfoveal choroidal thickness was increased to 274 µm in the left eye. OCT angiography revealed a blood flow signal within the pachydrusen. However, fluorescein and indocyanine green angiographies indicated no abnormal hyperfluorescent lesion in the macula of the left eye. During the 13-month follow-up, the blood flow signal in OCT angiography did not change in diameter, and no exudative change was observed. The blood flow signal may have properties of capillary blood vessels derived from the choriocapillaris, rather than angiogenic vessels from choroidal neovascularization or polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization.

Progression of age-related macular degeneration in eyes with abnormal fundus autofluorescence in a Japanese population: JFAM study report 3.

PURPOSE: To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD. METHODS: Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters. RESULTS: Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86). CONCLUSION: The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

Mental Status and Feasibility of an Intravitreal Ranibizumab Treat-and-Extend Regimen in Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) therapy is the first-choice treatment for neovascular age-related macular degeneration (nvAMD); however, patients often are burdened physically, financially, and mentally. We investigated the relationship between mental status and feasibility of an intravitreal ranibizumab treat-and-extend (TAE) regimen for nvAMD. METHODS: In this prospective, multicenter study, 75 patients with nvAMD received ranibizumab intravitreally in a TAE regimen. After two monthly injections, the injection intervals were extended step-by-step to 6, 8, 12, and 16 weeks in eyes with dry maculas on optical coherence tomography (OCT) and, if exudation persisted or relapsed, shortened by one step. The best corrected visual acuity (BCVA) measurement and OCT were performed at baseline and on the same days of the scheduled injections. At baseline, all patients completed a survey, the Hospital Anxiety and Depression Scale (HADS), regarding mental burden. At week 52, patients on the TAE regimen for 1 year completed the HADS and a questionnaire designated to assess treatment-associated mental status. RESULTS: Fifty-one patients (68%) completed the 1-year TAE regimen; 24 eyes (32%) discontinued the TAE regimen because of the rescue treatment, difficulty in completing clinical visits, or financial burden. In 51 eyes on the TAE regimen for 1 year, the mean BCVAs improved from 64.3 letters at baseline to 71.6 letters at week 52. The mean anxiety and depression scores on HADS decreased significantly (p < 0.01) after the 1-year treatment. Women tended to have higher anxiety scores, possibly associated with fear of injection and recurrence, while some men had higher depression scores potentially associated with financial burden, difficulty in completing clinical visits, and subsequent interruption of the TAE regimen especially in eyes with low treatment efficacy. CONCLUSIONS: A TAE regimen of intravitreal ranibizumab injections preserves vision in eyes with nvAMD and reduces mental burden associated with disease relapse. TRIAL REGISTRATION: This clinical study was registered retrospectively on December 22, 2014 with the ClinicalTrials.gov identifier NCT02321839.

Eosinophilic Granulomatosis with Polyangiitis Presenting with Central Retinal Artery Occlusion During Treatment with Anti-interleukin-5 Receptor Monoclonal Antibody.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophilic cytoplasm antibody (ANCA)-associated vasculitis characterized by asthma and eosinophilia. Although EGPA involves multiple organs, ocular involvement is infrequent and often carries a poor visual prognosis. We herein report a rare case of EGPA presenting with central retinal artery occlusion (CRAO) in which visual loss developed during treatment with anti-interleukin (IL)-5 receptor monoclonal antibody, and improvement in visual outcomes was attained after treatment combining high-dose oral corticosteroids, cyclophosphamide and an anticoagulant. Physicians should consider CRAO as an ophthalmic manifestation of EGPA in patients with severe eosinophilic asthma.

Twenty-Four Month Results of Intravitreal Ranibizumab for Macular Edema after Branch Retinal Vein Occlusion: Visual Outcomes and Resolution of Macular Edema.

Purpose: To report 24-month results after one intravitreal ranibizumab (IVR) injection followed by pro re nata (PRN) dosing for macular edema (ME) after branch retinal vein occlusion (BRVO).Methods: Eyes with BRVO met the followings were included: 77 letters or less best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] score) and central retinal thickness (CRT) of 250 µm or more. IVR injection was performed followed by a PRN regimen. The retreatment criteria included visual loss of five or more ETDRS letters compared with the previous visit, 250 µm or more of CRT, or presence of residual or recurrent ME including the parafoveal lesions. The primary outcome measures were the BCVA changes at month 12 and month 24 from baseline, and the secondary outcomes were changes in CRT, resolution of ME, the number of IVR injections, and changes of nonperfused areas (NPAs).Results: Twenty eyes of 20 patients (5 men, 15 women; mean age, 68.2 years) were enrolled. The mean BCVAs (ETDRS letters) at baseline, month 12, and month 24 were 62.0, 80.2, and 80.9, respectively. The mean ETDRS letters gains were 18.3 and 19.0 at month 12 and month 24, respectively. The percentages of patients with Snellen equivalent BCVAs of 20/20 or better at month 12 and month 24 were 75% and 70%, respectively. The mean CRTs at baseline, month 12, and month 24 were 480, 252, and 272 µm, respectively. Forty percent of all eyes had complete resolution of ME. The mean number of IVR injections was 8.3 times, which gradually decreased over time. The NPA change in either Zone 1 or Zone 2 was not significant during the follow-up. No adverse side effects were observed.Conclusion: IVR injection followed by a PRN regimen provided pretty good visual outcomes at month 24.

Ten-year changes in visual acuity at baseline and at 2 years after treatment in a Japanese population with age-related macular degeneration.

PURPOSE: We investigated 10-year changes in baseline best-corrected visual acuity (BCVA), as well as functional and anatomical changes at 1 and 2 years after initial treatment, in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD). METHODS: This retrospective, multicenter, case series reviewed patients with treatment-naïve nAMD who underwent initial treatment from 2006 to 2015, using photodynamic therapy (PDT), anti-vascular endothelial growth factor (VEGF), or a combination of PDT and anti-VEGF. BCVA and central retinal subfield thickness (CRST), were measured at baseline and at 1 or 2 years of follow-up. RESULTS: In total, 3096 eyes of 3096 patients were included from 14 hospitals. Mean BCVA at baseline became significantly better over the 10-year study period (P < 0.001). BCVA at 1 year significantly improved from baseline in patients who underwent initial treatment from 2009 to 2015 (P = 0.001, 2009; P = 0.004, 2010; P = 0.01, 2011; P < 0.001, 2012-2015). BCVA at 2 years significantly improved from baseline in patients who underwent initial treatment from 2012 to 2015 (P < 0.001, 2012; P < 0.001, 2013-2015). CRST at 1 year decreased significantly from CRST at baseline, each year from 2006 to 2015 (P < 0.001, 2006-2015). CRST at 2 years decreased significantly from CRST at baseline, each year from 2006 to 2015 (P = 0.03, 2006; P < 0.001, 2007-2015). CONCLUSION: Baseline BCVA with treatment-naïve nAMD tended to become better during the study period. BCVA at 1 year improved in the era of anti-VEGF; BCVA at 2 years improved in patients who underwent initial treatment in 2012 or later; and CRST decreased in each year during the study period.

Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics.

Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.

Bilateral giant retinal pigment epithelial tears in hypertensive choroidopathy.

PURPOSE: To report a case of hypertensive choroidopathy with bilateral bullous serous retinal detachments (SRDs), retinal pigment epithelial detachments (PEDs), and giant retinal pigment epithelial (RPE) tears. OBSERVATIONS: A 68-year-old man with a history of hypertension and diabetes mellitus presented with bilateral visual loss of about 10 day's duration. He discontinued his oral medications for 2 months without the advice of a physician. At his first visit, the best-corrected visual acuities (BCVAs) were 0.02 in the right eye and 0.3 in the left eye (decimal notation), and the respective intraocular pressures were 15 and 13 mmHg. Bullous SRDs, large PEDs, and giant RPE tears were present bilaterally. Blot retinal hemorrhages and hard exudates were seen in the left eye. The systemic blood pressure was 231/77 mmHg, and bilateral lower leg edema was observed. Biochemical blood tests showed deteriorated renal function, hypoalbuminemia, and hyperglycemia. Ultra-wide-field fundus fluorescein angiography showed leakage at the areas of the SRDs and hyperfluorescent areas corresponding to the RPE tears bilaterally. Indocyanine green angiography showed hypofluorescent areas corresponding to the PEDs. Systemic computed tomography and magnetic resonance imaging were performed, and no malignancy was found. Based on these findings, hypertensive choroidopathy was diagnosed. A week after antihypertensive treatment, the SRDs and PEDs resolved bilaterally, and the BCVAs improved to 0.4 and 0.5 in the right and left eyes, respectively. The RPE tears remained in both eyes, although the SRDs and PEDs did not recur. CONCLUSIONS AND IMPORTANCE: Hypertensive choroidopathy must be considered in the differential diagnosis of SRDs and/or PEDs.

Tilted Disc Syndrome Associated with Serous Retinal Detachment: Long-term Prognosis. A Retrospective Multicenter Survey.

PURPOSE: This study evaluated the long-term visual prognosis of a serous retinal detachment (SRD) secondary to tilted disc syndrome with or without an SRD at the final visit and the interventions. DESIGN: A retrospective, observational case series. METHODS: This was a multicenter study with an enrollment of 48 eyes of 41 treatment-naïve patients (14 men, 27 women) in whom tilted disc syndrome-related SRD was diagnosed at the first visit. Investigators at each institution decided whether to observe the patients without interventions or to treat with intravitreous injections of antivascular endothelial growth factor agents, photodynamic therapy, or both therapies combined. The patients were followed for at least 12 months. Main outcome measurements were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline. RESULTS: Analyses of all eyes showed improvement from baseline when BCVA was measured (P < 0.0001), although last BCVA was similar to BCVA at baseline (P = 0.46). CRT significantly improved from that at baseline at the final visit (P < 0.0001). When eyes with or without SRD at the final visit were analyzed, baseline BCVAs (P = 0.22) were similar, whereas BCVA (P = 0.05) and last BCVA (P = 0.005) were significantly better in eyes without SRD. When eyes with or without the interventions were analyzed, baseline (P = 0.70), best (P = 0.99), and last (P = 0.70) BCVAs were similar. Last CRT significantly decreased from baseline CRT in eyes that had undergone interventions (P < 0.0001). CONCLUSIONS: The visual prognosis of SRD secondary to tilted disc syndrome was better when SRD resolved but was not influenced by the treatments.

Central serous chorioretinopathy with and without steroids: A multicenter survey.

We investigated the rates of the use of steroids in Japanese central serous chorioretinopathy (CSC) cases and differences in the characteristics of CSC with and without steroids. A total of 538 eyes of 477 patients diagnosed with CSC, with 3 months or more of follow-up between April 2013 and June 2017 at 8 institutions. Patients with CSC with more than 3 months of follow-up were identified by OCT and fluorescein angiography at 8 institutions. Data collected included patient demographics, history of corticosteroid medication and smoking, spherical errors, findings of angiography, subfoveal choroidal thickness, and changes through the follow-up period. Differences in these findings were analyzed in cases with and without corticosteroid treatment. Among the 477 patients (344 men,133 women), 74 (15.5%) (39 men, 35 women) underwent current or prior steroid treatment. Cases with steroids were higher age (p = 0.0403) and showed no male prevalence, more bilateral involvement (p < 0.0001), and the affected eyes had multiple pigment epithelial detachment (p <0.0001), more fluorescein leakage sites (p < 0.0001), greater choroidal thickness (p = 0.0287) and a higher recurrence rate (p = 0.0412). Steroids can cause severer CSC through an effect on choroidal vessels and an impairment of retinal pigment epithelium.

Fundus autofluorescence and retinal sensitivity in fellow eyes of age-related macular degeneration in Japan.

PURPOSE: Abnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD. METHODS: Sixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as "within," "close," and "distant," based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated. RESULTS: In Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF. CONCLUSION: In Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.