Improvements of Retinal Sensitivity after Intravitreal Injection of Aflibercept in Eyes with Neovascular Age-Related Macular Degeneration with or without Polypoidal Choroidal Vasculopathy.

PURPOSE: We aim to determine the effects of intravitreal aflibercept (IVA) on the mean sensitivity (MS) of the central retina, best-corrected visual acuity (BCVA), and central foveal thickness (CFT) in eyes with neovascular age-related macular degeneration (nAMD) with or without polypoidal choroidal vasculopathy (PCV). METHODS: This was a prospective, interventional study. All eyes were treatment-naive with nAMD with or without PCV. Each eye received 3 monthly IVA injections followed by an IVA injection every 2 months for 12 months. The primary outcome was the change in the MS within the central 2°. The secondary outcomes were the changes in BCVA, CFT, greatest linear dimension (GLD), and percentage of eyes with a dry macula. RESULTS: Thirty-seven eyes of 37 patients were studied. A significant improvement of the MS (dB) was observed +4.9 ± 4.6 dB (mean ± standard deviation) at 3 M (p < 0.001), +5.5 ± 4.9 dB at 6 (p < 0.001), and +7.0 ± 3.4 dB at 12 M (p < 0.001) compared to the baseline in all eyes. The MS of the eyes with non-PCV was not significantly different from that of eyes with PCV (p = 1.00, 1.00, 1.00, and 0.76 at baseline, 3, 6, and 12 M, respectively). The MS of 11 patients whose BCVA remained unchanged was significantly improved by +6.5 ± 2.8 dB at 3 M (p < 0.001), +6.1 ± 4.3 dB at 6 M (p < 0.001), and +6.4 ± 4.8 dB at 12 M (p = 0.003) compared to the baseline. The mean BCVA was significantly improved from the baseline to 3 M (p < 0.001), 6 M (p = 0.027), and 12 M (p = 0.003) in all eyes. The BCVA was improved or maintained in 97% of the patients at 12 M. The mean CFT and GLD were significantly reduced at 12 M (p < 0.001). Twenty-two eyes (71%) had a dry macula at 12 M. CONCLUSIONS: IVA administered by a fixed dosing regimen led to significant improvements of the central MS, BCVA, and macular morphology at 1 year in eyes with nAMD with or without PCV. These results were not significantly different between eyes with non-PCV and with PCV. The improvements of the MS of the retina of the central 2° in a subgroup whose BCVA remained unchanged through the 12-month experimental period was also significant. We conclude that the MS of the central 2° might be a better marker than the BCVA in determining the effectiveness of IVA treatments and might be helpful in determining early effects on the retina before BCVA changes can be detected.

Surgical outcomes of vitrectomy for breakthrough vitreous hemorrhage in eyes with exudative age-related macular degeneration.

PURPOSE: To report the outcomes of pars plana vitrectomy in cases with breakthrough vitreous hemorrhage (VH) secondary to exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy. We also investigated the relationship between the preoperative b-mode ultrasonographic findings and the postoperative visual acuity to determine if the ultrasonographic findings can predict the surgical outcome after pars plana vitrectomy. METHODS: This was a retrospective, interventional, case series. Twenty eyes of 20 patients were studied. The associations between the pre- and intraoperative factors and the final best-corrected visual acuity (BCVA) were determined. Recombinant tissue-plasminogen activator (tPA) was used in cases with massive hemorrhagic retinal detachment. RESULTS: Ten eyes with polypoidal choroidal vasculopathy (PCV), two eyes with choroidal neovascularization (CNV), and eight eyes with an unknown type of AMD were studied. The mean BCVA was 0.73 ± 0.57 logarithm of the minimum angle of resolution (logMAR) units before developing the VH, 2.25 ± 0.45 logMAR units before the surgery, and 1.52 ± 0.87 logMAR units after the surgery. The BCVA improved significantly after the surgery (P = 0.004) but was significantly worse than that before developing the VH (P = 0.012). The cases of PCV had better final BCVA than cases of CNV (P = 0.043, Mann-Whitney test). The preoperative presence of a subretinal elevation at the macula detected by ultrasonography was significantly associated with a poorer final BCVA (P = 0.031). CONCLUSIONS: Vitrectomy significantly improved visual function in the eyes with VH associated with exudative AMD. The eyes with PCV and no macular subretinal elevation on ultrasonography had a better visual prognosis.

Long-Term Effects of Half-Time Photodynamic Therapy on Retinal Sensitivity in Eyes with Chronic Central Serous Chorioretinopathy.

The purpose of this study was to evaluate the long-term effects of half-time photodynamic therapy (PDT) on the retinal sensitivity in eyes with chronic central serous chorioretinopathy (CSC). Twenty-two eyes of 22 patients with chronic CSC were studied. PDT was applied with full-dose verteporfin and half-time laser duration. The best-corrected visual acuity (BCVA) and retinal sensitivity in the central 2 and 10 degrees were evaluated at the baseline, and at 12 and 24 months after the half-time PDT. The retinal sensitivity was determined by Macular Integrity Assessment microperimetry (MAIA, Centervue, Padova, Italy). The results showed that the mean retinal sensitivities in the central 2 and 10 degrees were significantly improved at 12 months (25.6 ± 2.79 dB, median; 26.11 dB, 25.6 ± 2.25 dB, median; 25.65 dB, respectively; P < 0.001) and at 24 months (26.3 ± 2.62 dB, median; 27.38 dB, 26.6 ± 2.21 dB, median; 27.45 dB, respectively; P < 0.001) after the treatment compared to that at the baseline (19.2 ± 3.93 dB, median; 19.34 dB, 20.9 ± 2.92 dB, median; 20.9 dB, respectively). The BCVA was also significantly improved from 0.18 ± 0.19 median; 0.15 logarithm of the minimum angle of resolution (logMAR) units at the baseline to 0.07 ± 0.15 median; 0 logMAR units at 12 months (P < 0.001) and to 0.049 ± 0.16 median; -0.039 logMAR units at 24 months (P < 0.001). We conclude that half-time PDT results in a significant improvement of the mean central retinal sensitivity for at least 24 months in eyes with chronic CSC. Thus, half-time PDT is beneficial in resolving chronic CSC for a relatively long period.

Safety and Efficacy of Ranibizumab and Luseogliflozin Combination Therapy in Patients with Diabetic Macular Edema: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

INTRODUCTION: Diabetic macular edema (DME) threatens daily life activities such as reading and driving and reduces the patients' quality-of-life. Recently, anti-vascular endothelial growth factor (VEGF) agents have become a first-line therapy in DME. However, therapy with anti-VEGF agents has several problems: repeated invasive injections are required; medical costs are high; and a certain proportion of patients with DME are resistant to treatment with anti-VEGF agents. While sodium-glucose co-transporter 2 (SGLT2) inhibitors have been widely used for the treatment of type 2 diabetes mellitus (T2DM), the effects of a combination therapy with anti-VEGF agent and SGLT2 inhibitor on DME are not yet known. METHODS: This study enrolls subjects with T2DM and DME, randomizes them into either a study agent treatment group (treated with ranibizumab as anti-VEGF agent and luseogliflozin as SGLT2 inhibitor) or a control group (treated with ranibizumab and glimepiride), and observes the subjects for 52 weeks after initiation of treatment. Planned outcomes: The primary endpoint is intergroup difference in the number of intravitreal anti-VEGF injections to the study eye from baseline to week 48. Secondary and exploratory endpoints include safety and ophthalmologic and internal medical clinical parameters. REGISTRATION: This study is registered at the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961) and Japan Registry of Clinical Trials (jRCTs031180210).

Pneumatic displacement with intravitreal bevacizumab for massive submacular hemorrhage due to polypoidal choroidal vasculopathy.

BACKGROUND: The purpose of this study was to compare the effectiveness of pneumatic displacement combined with intravitreal bevacizumab (IVB) with that of pneumatic displacement (PD) alone to treat massive submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). METHODS: Thirty-two eyes of 32 patients with massive SMH secondary to PCV were studied. Twenty-two eyes were treated with a combination of PD and 1.25 mg of intravitreal bevacizumab (PD + IVB group), and ten eyes with pneumatic displacement alone (PD group). RESULTS: Pretreatment, the differences in best-corrected visual acuity and size of the SMH between the two groups were not significant (P=0.59 and P=0.72, respectively). Complete displacement of the hemorrhage from under the fovea was achieved in 19 of 22 eyes (86.4%) in the PD + IVB group and in five of ten eyes (50%) in the PD group. The best-corrected visual acuity in the PD + IVB group was significantly better than that in the PD group at one, 3, and 6 months after treatment (P<0.001, P<0.001, and P<0.001, respectively). Improvement in best-corrected visual acuity by >0.3 logMAR units was obtained in 18 eyes (81.8%) in the PD + IVB group and two eyes (20%) in the PD group (P<0.001). The number of eyes that required additional treatments was significantly fewer in the PD + IVB group than in the PD group (P=0.0001). CONCLUSION: The combination of PD and IVB may be a better therapeutic procedure for eyes with massive SMH due to PCV in the short term because of the better visual outcome and less need for additional treatments.

Werner syndrome with refractory cystoid macular edema and immunohistochemical analysis of WRN proteins in human retinas.

BACKGROUND: To present our findings in a case of Werner syndrome with refractory cystoid macular edema (CME) and to determine the expression and the distribution of WRN proteins in human retinas. CASE PRESENTATION: A 35-year-old man with Werner syndrome who developed CME after YAG laser treatment was studied. Optical coherence tomographic (OCT) scans were used to examine the CME in the right eye. The patient received topical eye drops (0.1% bromfenac sodium hydrate twice daily and 1% dorzolamide hydrochloride thrice daily), sub-Tenon triamcinolone injection thrice, intravitreal bevacizumab injection twice, and pars plana vitrectomy of the right eye. Genetic analyses were performed to diagnose the disease. To examine the expression and distribution of WRN proteins in the retinas, immunohistochemistry for WRN proteins was performed in human retinas. The CME in the right eye was not improved by any of the treatments. During the follow-up period, CME developed in the left eye. Genetic analyses detected compound heterozygosity, Mut4 and Mut11, in the WRN gene and the individual was diagnosed with Werner syndrome. Immunohistochemical analysis of WRN proteins expression in human retinas showed that WRN proteins were expressed in the parts of the Müller cells in the inner nuclear layer and outer nuclear layer. CONCLUSION: Patients with Werner syndrome can develop severe CME after laser treatment. A pathological link may exist between mutations in the WRN gene and the development of CME in patients with Werner syndrome.

One-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy (RF-PDT) to intravitreal ranibizumab (IVR) alone for eyes with polypoidal choroidal vasculopathy (PCV). METHODS: We reviewed the medical records from 47 consecutive patients with PCV (47 naïve eyes). Seventeen eyes from 17 patients had one IVR treatment combined with RF-PDT followed by two additional IVR treatments (combined group), and 30 eyes from 30 patients were treated with 3 monthly IVR treatments (IVR group). All eyes had a follow-up period of at least 12 months. RESULTS: At 12 months, the mean logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) significantly improved from 0.55 to 0.38 logMAR units in the combined group (P=0.041) but did not change significantly in the IVR group (P=0.371). The central foveal thickness (CFT) was significantly thinner in both groups at 6 months (P<0.01). Additional IVR injections were required less frequently in the combined group (n=3; 17%) than in the IVR group (n=16; 53%) during the 12 month follow-up (P=0.029). CONCLUSION: The IVR and RF-PDT combination led to significant BCVA improvements and required fewer additional IVR treatments for at least 12 months in eyes with PCV.

Retinal pigment epithelium tear after vitrectomy for vitreomacular traction syndrome in an eye with retinal angiomatous proliferation.

An 87-year-old Japanese man presented with retinal angiomatous proliferation (RAP) and a retinal pigment epithelium (RPE) detachment in his right eye. His decimal best-corrected visual acuity was 0.15 in the right eye, and optical coherence tomography (OCT) showed a vitreomacular adhesion in the right eye as well. After 3 monthly intravitreal injections of ranibizumab, the size and height of the RPE detachment was significantly reduced. The accumulated intra- and subretinal fluid also disappeared, but the vitreomacular traction remained. Pars plana vitrectomy was performed, and the posterior hyaloid was separated from the retina with a vitrectomy cutter without any intraoperative complications. Two months after the surgery, a large RPE tear was observed over the macular area. His visual acuity decreased to 0.06 and remained unchanged thereafter. We suggest that the small tear led to the larger RPE tear because vitreomacular traction was transmitted to the RPE through the fibrovascular tissue of the RAP during the creation of the hyaloid detachment. Because such an RPE tear has not been reported after vitrectomy for vitreomacular traction, surgeons need to pay special attention to this potential complication in eyes with vitreomacular traction and RAP.

Two-year course of subfoveal pigment epithelial detachment in eyes with age-related macular degeneration and visual acuity better than 20/40.

PURPOSE: To investigate the course of subfoveal pigment epithelial detachments (PEDs) in eyes with age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) ≥20/40. METHODS: Thirty-seven eyes of 35 patients with a subfoveal PED were divided into an avascular PED group (n = 11), a vascularized PED group due to polypoidal choroidal vasculopathy (PCV, n = 14) and an occult choroidal neovascularization (CNV) group (n = 12). Intravitreal bevacizumab or ranibizumab was given as needed. The BCVA, central foveal thickness, PED thickness, and lesion size were measured at baseline and at 2 years after the initial examination. RESULTS: The BCVA did not change significantly in the avascular group, decreased from 0.06 ± 0.11 to 0.23 ± 0.15 logMAR units in the PCV group and from 0.12 ± 0.12 to 0.71 ± 0.70 logMAR units in the CNV group. At 2 years, the central foveal and PED thicknesses were not significantly different among the 3 groups, and the lesion was significantly larger in the PCV and CNV groups than in the avascular group. CONCLUSIONS: The vascularized PED cases had a poorer visual outcome than avascular PEDs with anti-VEGF drugs at the 2-year follow-up.

Long-term success of intravitreal bevacizumab for choroidal neovascularization associated with choroidal osteoma.

PURPOSE: To describe a case of choroidal osteoma with choroidal neovascularization (CNV) that was successfully treated with two intravitreal injections of bevacizumab (IVB). DESIGN AND METHODS: Case report on a 12-year-old Japanese girl who presented with a sudden decrease in vision in her left eye. At the first visit, 2 days after the onset of her symptoms, her visual acuity (VA) in her left eye was 0.2. Ophthalmoscopy showed a hemorrhage of 5 disc diameters under the retinal pigment epithelium and a serous retinal detachment at the posterior pole of the left eye. These findings were confirmed by optical coherence tomography. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) showed several points of leakage around the fovea, which suggested a CNV. From these findings, the patient was diagnosed with choroidal osteoma with a CNV. The submacular hemorrhage was from the CNV associated with the choroidal osteoma. We treated her with two injections of 1.25 mg/0.05 mL IVB with a 4-month interval. RESULTS: The patient's VA in her left eye improved to 0.7, and this vision was maintained for 4 years. The CNV disappeared in the FA and ICGA images and no recurrence was observed after 4 years. CONCLUSION: Our findings indicate that IVB is effective in resolving CNV in eyes with an osteoma and prevents a decrease of vision in eyes with a choroidal osteoma with a CNV.

Subretinal hemorrhage after photodynamic therapy for juxtapapillary retinal capillary hemangioma.

A 75-year-old Japanese woman presented with a juxtapapillary retinal capillary hemangioma (RCH) in her left eye. Twelve months after the initial examination, the size of the hemangioma had increased and the exudation from the RCH involved the macula. Her best-corrected visual acuity (BCVA) had decreased from 0.8 to 0.3. A total of five intravitreal injections of bevacizumab (IVB; 1.25 mg) was given but the RCH did not respond. A photodynamic therapy (PDT) was done using multiple laser spots to avoid damaging the optic nerve head. After the first PDT, the subfoveal fluid was reduced but not completely gone. One week after the second PDT, a massive subretinal hemorrhage developed. The subretinal hemorrhage was successfully displaced by injecting intraocular sulfur hexafluoride (SF(6)) gas. At the 3-year follow-up examination, no subretinal hemorrhage or fluid was observed at the macula and the BCVA remained at 0.05. Our case was resistant to the combination of anti-vascular endothelial growth factor (VEGF) and PDT and had a rare massive subretinal hemorrhage. A further collection of RCH cases treated with anti-VEGF and PDT that would justify this treatment is necessary.

Comparison of intravitreal bevacizumab to photodynamic therapy for polypoidal choroidal vasculopathy: short-term results.

AIMS: To compare the short-term therapeutic effects of intravitreal bevacizumab (IVB) to those of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). MATERIALS AND METHODS: Retrospective interventional case study. Eighty-nine eyes of 89 patients with symptomatic PCV were treated by IVB or PDT. Eighteen eyes were treated with a single injection of IVB (s-IVB group), 22 eyes with three consecutive monthly IVB injections (m-IVB group), and 49 eyes with PDT alone (PDT group). The best-corrected visual acuity (BCVA) and OCT-determined central foveal thickness (CFT) were evaluated before, and one and three months after the treatment. For statistical analyses, one-factor ANOVA and Chi-square test were used. RESULTS: The differences in the BCVA and CFT among the three groups at the baseline were not significant (P=0.992, P=0.981, respectively). Three months after the treatment, the BCVA improved by> 0.2 logMAR units in two out of 18 eyes (11%) in the s-IVB group, three out of 22 eyes (14%) in the m-IVB group, and 15 out of 49 eyes (31%) in the PDT group (P=0.124). A decrease in the CFT by> 20% was achieved in six out of 18 eyes in the s-IVB group, ten eyes (46%) in the m-IVB group, and 35 eyes (71%) in the PDT group (P=0.009). The resolution of polyps was achieved in three out of 18 eyes in the s-IVB group, one eye (5%) in the m-IVB group and 35 eyes (71%) in the PDT group (P < 0.001). CONCLUSION: The better short-term therapeutic outcomes in the PDT group than in the s-IVB and m-IVB groups indicate that PDT may be more effective than IVB in short term after treatment for PCV.

Two-year comparison of photodynamic therapy and intravitreal bevacizumab for treatment of myopic choroidal neovascularisation.

AIM: To compare the long-term outcome of photodynamic therapy (PDT) with that of intravitreal bevacizumab (IVB) for myopic choroidal neovascularizations (mCNVs). METHODS: 24 eyes were selected from 40 consecutive patients with mCNV, and the patients were divided into Group A, consisting of 12 eyes treated by PDT, and Group B, consisting of 12 eyes treated by 1.25 mg IVB. The age and best-corrected visual acuity (BCVA) were matched between the two groups. The BCVA, size of the chorioretinal atrophy surrounding the CNV (CRA), central foveal thickness (CFT) and CNV thickness were determined before and at 12 and 24 months after the treatment. RESULTS: The BCVA did not change after PDT but was significantly improved from 0.75+/-0.25 to 0.49+/-0.42 logMAR units at 12 months and to 0.50+/-0.38 logMAR units at 24 months after IVB. The CFT were significantly reduced in both groups at 12 and 24 months. The CRAs were larger in group A than in group B at 12 and 24 months, and their sizes were correlated with the BCVA. CONCLUSION: At 24 months, IVB is more effective than PDT in treating mCNV. The enlargement of the CRA might be related to the incomplete visual recovery after PDT.

Changes in visual function and thickness of macula after photodynamic therapy for age-related macular degeneration.

PURPOSE: To determine the correlation between the changes in the central retinal sensitivity and the changes in the foveal thickness (FT) after photodynamic therapy (PDT) for age-related macular degeneration (AMD). METHODS: Nineteen eyes of 19 patients with choroidal neovasularizations (CNVs) secondary to AMD were studied. The pretreatment values of the central retinal sensitivity determined by Micro Perimeter 1 (MP1; Nidek Technologies), best-corrected visual acuity (BCVA), and optical coherence tomography (OCT)-determined FT were compared to the postoperative values at three and six months after PDT. RESULTS: At six months, the retinal sensitivity within the central 10 degrees was significantly improved (P = 0.02) and the FT was significantly thinner (P = 0.016). The BCVA, however, did not change significantly (P = 0.80). The changes in the retinal sensitivities were significantly correlated with the changes in the decrease in the FT (r = - 0.59, P = 0.012 within the central 10 degrees ) at six months after PDT. CONCLUSION: Significant improvements in retinal sensitivities within the central 10 degrees and a decrease in FT were observed even though the BCVA was not significantly improved. The measurement of retinal sensitivity by MP1 may be a better method to assess central visual function than the conventional visual acuity after PDT.

Age-related macular degeneration with massive subretinal hemorrhage easily removed through a retinal break.

PURPOSE: To report a case of age-related macular degeneration (AMD) with massive subretinal hemorrhage easily removed through a retinal break. CASE REPORT: A 57-year-old Japanese man with a massive subretinal hemorrhage in an eye with AMD developed a rhegmatogenous retinal detachment after intraocular gas injection. The subretinal hemorrhage was easily removed using perfluorocarbon liquid during vitrectomy, and the retinal degeneration was minimal. CONCLUSION: Rhegmatogenous retinal detachment is an unfavorable complication after intraocular gas injection for the treatment of AMD. In our case, the subretinal hemorrhage was easily removed, and visual recovery was possible to some degree.