24-Hour Intraocular Pressure Fluctuation Suppressed by Microhook Trabeculotomy in Ocular Hypertension: A Case Report.

A 76-year-old woman was referred to our hospital for evaluation of markedly high intraocular pressures (IOPs): ≥40 mmHg in both eyes. No intraocular inflammation, pseudoexfoliation, or glaucomatous optic neuropathy was observed on ophthalmological examination. The 24-hour IOP fluctuations, measured with a Goldmann tonometer in the sitting position at 8, 12, 16, 20, and 24 o' clock, were 22/17, 33/28, 41/33, 30/22, and 30/24 mmHg, respectively, and showed a peak in the afternoon. The patient was diagnosed with ocular hypertension, and microhook trabeculotomy (µLOT) (right eye with lens reconstruction, left eye initially pseudophakic) was performed. After µLOT surgery in both eyes (4 days postoperatively in the right eye and 1 day postoperatively in the left eye), IOP decreased in both eyes to 12/15, 11/14, 12/15, 10/11, and 10/10 mmHg, and the fluctuation range was suppressed. At 3 months postoperatively (measured at 8, 12, 16, 20, 24, and 4 o' clock), the effect was maintained at 14/15, 15/19, 14/19, 11/12, 13/14, and 13/13 mmHg, respectively, but was slightly attenuated. In a patient with marked 24-hour IOP fluctuation, µLOT was effective in reducing IOP values and fluctuation.

Debilitating ocular globe rupture due to a forklift accident: A case report.

We describe a case of globe rupture due to a forklift accident. A 64-year-old man presented to the ophthalmology hospital shortly after the jaws of a forklift struck his left eye. The left eye was shrunken with a full-thickness scleral laceration. B-scan ultrasonography revealed a hypotonic eyeball with antero-posterior shrinkage. We promptly performed scleral suturing to maintain the ocular shape. The patient's intraocular pressure improved to 7.1 mmHg, and visual acuity was limited to light perception. Despite this, intraocular hemorrhage in the anterior chamber persisted, and an electroretinogram demonstrated poor response to light. Subsequently, the patient underwent a vitrectomy with silicone oil tamponade to address the vitreous hemorrhage, proliferative membranes, and retinal detachment. However, proliferative vitreoretinopathy with tractional retinal detachment progressed postoperatively, resulting in the loss of light perception. Ocular trauma caused by forklifts accident is rare; however, the strong external forces they exert can cause severe and irreversible visual impairment. Therefore, it is necessary for forklift operators and other concerned individuals to exercise caution to prevent forklift-related ocular trauma. Moreover, ophthalmologists should be aware of the dangers of forklift-related ocular trauma and treatment and management of the same.

Visual functions and multimodal imaging of patients with idiopathic focal choroidal excavation.

This study aimed to evaluate visual function and perform multimodal imaging on patients with focal choroidal excavation without any chorioretinal disease (idiopathic focal choroidal excavation [iFCE]). Seventeen eyes of 15 patients with iFCE (8 men, 7 women; mean ± standard deviation age, 56.0 ± 10.8 years) were assessed for visual function including visual acuity, metamorphopsia, aniseikonia, and retinal sensitivity. Multimodal imaging included optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography. This study found that the maximum width and depth of the excavation were 597 ± 330 (238-1809) µm and 123 ± 45 (66-231) µm, respectively, and that FAF showed normal or hypoautofluorescence corresponding to iFCE. The fundus examination findings were stable during the follow-up period (96 ± 48 months). None of the eyes showed any abnormalities in central retinal sensitivity or aniseikonia. Metamorphopsia was detected using Amsler grid testing and M-CHARTS in two eyes. Therefore, this study is the first to quantitatively and qualitatively study metamorphopsia of patients with iFCE. Our results showed that most patients with iFCE did not have visual impairments, despite the presence of morphological changes in the outer retina and choroid.

Trimebutine prevents corneal inflammation in a rat alkali burn model.

Alkaline burns to the cornea lead to loss of corneal transparency, which is essential for normal vision. We used a rat corneal alkaline burn model to investigate the effect of ophthalmic trimebutine solution on healing wounds caused by alkaline burns. Trimebutine, an inhibitor of the high-mobility group box 1-receptor for advanced glycation end products, when topically applied to the burned cornea, suppressed macrophage infiltration in the early phase and neutrophil infiltration in the late phase at the wound site. It also inhibited neovascularization and myofibroblast development in the late phase. Furthermore, trimebutine effectively inhibited interleukin-1ß expression in the injured cornea. It reduced scar formation by decreasing the expression of type III collagen. These findings suggest that trimebutine may represent a novel therapeutic strategy for corneal wounds, not only through its anti-inflammatory effects but also by preventing neovascularization.

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

Comparison of stereopsis and foveal microstructure after internal limiting membrane peeling and inverted internal limiting membrane flap techniques in patients with macular hole.

PURPOSE: To compare stereopsis and foveal microstructure after internal limiting membrane peeling and inverted internal limiting membrane flap technique in patients with macular hole. DESIGN: Retrospective observational study. METHODS: Sixty-six patients with macular hole were included, of whom 41 underwent 25-gauge pars-plana vitrectomy with complete internal limiting membrane peeling (Peeling group) and 25 with the inverted flap technique (Inverted group). We evaluated stereopsis using the Titmus Stereo Test and the TNO stereo test, best-corrected visual acuity, macular hole closure rate, and foveal microstructure with optical coherence tomography before and at 3, 6, and 12 months after surgery. MAIN OUTCOME MEASURES: Stereopsis and foveal microstructure. RESULTS: Preoperatively, no difference was observed in the base and minimum diameters of macular hole, Titmus Stereo Test score, TNO stereo test score, and best-corrected visual acuity between the Peeling and Inverted groups. The macular hole closure rate in the Peeling and Inverted groups were 97.6% and 100%, respectively, with no significant difference between groups. At 12 months postoperatively, Titmus Stereo Test score (2.1 ± 0.4 in the peeling and 2.2 ± 0.4 in the inverted groups), TNO stereo test score (2.3 ± 0.4 and 2.2± 0.5), and best-corrected visual acuity (0.20 ± 0.18 and 0.24 ± 0.25) were not significantly different between groups (p = 0.596, 0.332, respectively). The defect of the external limiting membrane was more common in the Inverted group than in the Peeling group at 6 months after surgery (5.4 vs. 28.0%; p < 0.05). No statistically significant inter-group differences were noted in the ellipsoid zone defect ratio throughout the follow-up period. CONCLUSIONS: There was no difference in postoperative stereopsis nor foveal microstructure between the internal limiting membrane peeling group and the inverted group in patients with macular hole.

Internal Limiting Membrane Peeling and Inverted Flap Technique in Macular Hole: Postoperative Metamorphopsia and Optical Coherence Tomography.

INTRODUCTION: We compared postoperative metamorphopsia and optical coherence tomography (OCT) findings between eyes that underwent internal limiting membrane (ILM) peeling and the inverted flap (IF) technique for macular hole (MH). METHODS: This retrospective analysis included 64 eyes of 64 patients with idiopathic MH whose MH was closed after initial surgery. Thirty-nine patients were treated with pars plana vitrectomy (PPV) with ILM peeling, and 25 patients were treated with PPV with the IF technique. Best corrected visual acuity (BCVA), severity of metamorphopsia, and OCT images were collected before and 3, 6, and 12 months postoperatively. Based on the OCT images, the status of the external limiting membrane (ELM) and ellipsoid zone and the presence of hyperreflective plugs were assessed. RESULTS: At baseline and 3, 6, and 12 months postoperatively, BCVA and severity of metamorphopsia were not significantly different between groups. The status of the ELM was significantly worse in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Significantly more hyperreflective plugs were observed in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Stepwise multiregression analysis revealed that hyperreflective plugs were significantly associated with the severity of metamorphopsia at 12 months postoperatively. DISCUSSION/CONCLUSION: The alterations on the OCT were fewer in the ILM peeling group than in the IF group, while no significant differences were observed in postoperative severity of metamorphopsia between groups. Metamorphopsia was worse in eyes with hyperreflective plugs.

Changes in Metamorphopsia in Patients Undergoing Treatment for Vitreoretinal Disorders.

PURPOSE: To quantify and compare the severity of metamorphopsia in patients undergoing vitrectomy for vitreoretinal disorders. METHODS: Data were collected evaluated from 319 patients with vitreoretinal disorders, including epiretinal membrane (ERM), macular hole (MH), cystoid macular edema with branch retinal vein occlusion (BRVO-CME), CME with central retinal vein occlusion (CRVO), diabetic macular edema (DME), macula-off rhegmatogenous retinal detachment (M-off RD), and macula-on RD (M-on RD). Metamorphopsia was recorded with the M-CHARTS preoperatively and at 3 and 6 months postoperatively. RESULTS: Preoperative and 6-month postoperative metamorphopsia scores were 0.69 ± 0.50 and 0.50 ± 0.52, respectively. Before surgery, 94% of patients presented with metamorphopsia (score ≥0.2). Preoperative metamorphopsia scores were significantly correlated with postoperative metamorphopsia scores (r = 0.378, p < 0.0001). Preoperative metamorphopsia score was significantly higher for ERM (0.89) than for DME (0.51). Vitrectomy significantly improved metamorphopsia in ERM and MH but not in the other disorders. In contrast, treatment improved visual acuity for all disorders except CRVO-CME and M-on RD. CONCLUSION: This quantitative study indicated that metamorphopsia is present in most patients undergoing surgery for vitreoretinal diseases and is most severe in ERM. In these patients, vitrectomy improved visual acuity but not metamorphopsia.

FIVE-YEAR VISUAL OUTCOME OF TREATMENT FOR RETINOPATHY OF PREMATURITY IN INFANTS WEIGHING <500 G AT BIRTH: A Multicenter Cohort Study From J-CREST.

PURPOSE: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies. METHODS: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment. RESULTS: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes. CONCLUSION: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.

Comparison of long-term treatment outcomes of laser and anti-VEGF therapy in retinopathy of prematurity: a multicentre study from J-CREST group.

OBJECTIVES: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP). METHODS: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses. RESULTS: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively). CONCLUSIONS: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment.

Vision-Related Parameters Affecting Stereopsis after Retinal Detachment Surgery.

Even after successful surgery, the stereopsis of retinal detachment (RD) patients is inferior to that of normal subjects. However, it is unclear which visual dysfunction in the affected eye is responsible for the postoperative stereopsis impairment. This study included 127 patients after successful surgery for unilateral RD. Stereopsis, best-corrected visual acuity (BCVA), severity of metamorphopsia, letter contrast sensitivity and amount of aniseikonia were examined at 6-month postoperatively. Stereopsis was assessed using the Titmus Stereo Test (TST) and TNO stereotest (TNO). Postoperative stereopsis (log) in patients with RD were 2.09 ± 0.46 in the TST and 2.56 ± 0.62 in the TNO. Multivariate analysis with stepwise regression revealed postoperative TST was associated with BCVA, and TNO was associated with BCVA, letter contrast sensitivity, metamorphopsia and absolute values of aniseikonia. In a subgroup analysis that selected those with more impaired stereopsis, postoperative TST was associated with BCVA (p < 0.001), and TNO was associated with letter contrast sensitivity (p < 0.005) and absolute values of aniseikonia (p < 0.05) by multivariate analysis. Deterioration of stereopsis after RD surgery was affected by a variety of visual dysfunctions. The TST was affected by visual acuity, while the TNO was affected by contrast sensitivity and aniseikonia.

Risk Factors for Legal Blindness in 237 Japanese Patients with Exogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Contrast sensitivity and quality of life following intravitreal ranibizumab injection for central retinal vein occlusion.

SYNOPSIS/PRECIS: We investigated the relationship between contrast sensitivity (CS) and vision-related quality of life (VR-QOL) in patients with central retinal vein occlusion following ranibizumab intravitreal injection; CS showed a stronger association with VR-QOL than visual acuity. BACKGROUND/AIMS: To investigate the relationship between CS, VR-QOL and optical coherence tomography (OCT) findings in patients with cystoid macular oedema secondary to central retinal vein occlusion (CRVO-CMO) following intravitreal injection of ranibizumab. METHODS: This was a multicentre, open-label, single-arm, prospective study. The study included 23 patients with CRVO-CMO who were followed up for 12 months after treatment. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS) and OCT images were obtained every month. For VR-QOL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was administered to the patients before treatment and at 3, 6 and 12 months following treatment. RESULTS: The LCS and VFQ-25 composite score improved significantly from baseline to 12 months following treatment. The multiple regression analysis revealed that the LCS of the affected eye and BCVA of the fellow eye were related to the VFQ-25 composite score following treatment. The LCS improvement showed a significant correlation with the improvement in the VFQ-25 composite score, whereas the BCVA improvement was not correlated with the improvement in the VFQ-25 composite score. Stepwise multiple regression analyses revealed that, at the time of macular oedema resolution, the distance between the external limiting membrane and retinal pigment epithelium (ELM-RPE) and average ganglion cell-inner plexiform layer (GCIPL) thickness were associated with LCS. CONCLUSION: CS had a stronger association with VR-QOL than with BCVA in patients with CRVO-CMO. With the resolution of macular oedema, CS was associated with ELM-RPE thickness and average GCIPL thickness.

Vision-related quality of life and subscale items following intravitreal ranibizumab injections for central retinal vein occlusion.

PURPOSE: To evaluate the vision-related quality of life (VR-QOL) before and after intravitreal ranibizumab injections (IVR) for central retinal vein occlusion (CRVO) and to investigate subscale items of VR-QOL in detail. STUDY DESIGN: A multicenter, open-label, prospective and comparative study. METHODS: Twenty-three patients with treatment naïve CRVO and 22 age-matched normal controls were included. VR-QOL was assessed by 25-Item Visual Function Questionnaire (VFQ-25) before and up to 12 months post-treatment. The VFQ-25 composite score and 12 subscales were compared between CRVO patients and normal controls. RESULTS: The VFQ-25 composite scores of CRVO patients showed significant improvement throughout the treatment period compared with baseline. The VFQ-25 composite scores both before and after treatment for CRVO were significantly lower than in normal controls. The subscale items, including general health, general vision, near activities, social functioning, mental health, role difficulties, dependency, and peripheral vision in CRVO, were significantly lower than in the normal controls even after treatment. CONCLUSION: Vision-related QOL was low in patients with CRVO before treatment and improved with IVR. In spite of the improvements, several subscale items remained lower than in normal controls following treatment. Attention should be paid to the patients with CRVO and their decreased visual, social and psychological QOL.

Changes in metamorphopsia following intravitreal aflibercept injection for diabetic macular edema.

The aim of the present study was to investigate changes in metamorphopsia in patients with diabetic macular edema (DME) following intravitreal aflibercept injection (IVA) with the treat and extend (TAE) regimen for a year. We performed a post hoc analysis of a multicenter, open-label, single-arm, prospective study. The study included 20 patients with DME. All eyes received 3 monthly loading injections of 2 mg aflibercept, followed by a TAE regimen. Every visit, the severity of metamorphopsia and the best-corrected visual acuity (BCVA) were evaluated, and optical coherence tomography (OCT) images were obtained. The severity of metamorphopsia was measured using M-CHARTS. The metamorphopsia scores before treatment and at 1, 2, 3, 6 and 12 months following treatment were 0.25 ± 0.23, 0.21 ± 0.15, 0.19 ± 0.23, 0.14 ± 0.16, 0.17 ± 0.20 and 0.10 ± 0.17, respectively, with significant improvement from before treatment to 3 and 12 months following treatment (p < 0.05 and p < 0.005, respectively). At the time of macular edema resolution, the presence of an epiretinal membrane (ERM) was associated with the metamorphopsia score (p < 0.05). In conclusion, the metamorphopsia score in patients with DME improved following IVA with the TAE regimen for one year. The presence of ERM was associated with the metamorphopsia score.

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.

Time course of changes in vision-related quality of life following intravitreal ranibizumab treatment for branch retinal vein occlusion.

To evaluate the vision-related quality of life (VR-QOL) treated by intravitreal ranibizumab (IVR) in patients with branch retinal vein occlusion (BRVO) and to assess subscale items of the VR-QOL. This was prospective, multicenter, open-label, observational study including 38 patients with unilateral BRVO who underwent IVR treatment and 28 age-matched healthy subjects. VR-QOL using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and best-corrected visual acuity (BCVA) were examined before and at 3, 6, and 12 months after treatment. The VFQ-25 composite score and BCVA significantly improved from 3 to 12 months after IVR treatment (P < 0.05), such that there was no significant difference between the BRVO and control groups at 12 months. All subscales of the VFQ-25, except "general health", significantly improved after treatment, while "near vision" and "mental health" were worse than those in healthy subjects (P < 0.05). Patients with superior BRVO had a lower "near vision" score than healthy subjects after treatment (P < 0.05). BCVA in the treated eye and fellow eye had no significant relationship with the VFQ-25 composite score before and after treatment. The VR-QOL of patients with BRVO improved with IVR treatment and was comparable to that of healthy subjects after 12 months. Superior BRVO particularly affected near vision for a low level.

Analysis of the sustained release ability of bevacizumab-loaded tetra-PEG gel.

Multiple intravitreal injections, which are painful and costly, are often required in the treatment of retinal disorders. Therefore, a novel drug delivery system using hydrogels is currently being evaluated as an alternative. This study aimed to evaluate the ability of tetra-armed polyethylene glycol (tetra-PEG) gel for sustained release in vitro. Bevacizumab-loaded tetra-PEG gel and 5-Carboxyfluorescein N-succinimidyl ester (FAM-NHS)-labeled IgG-loaded tetra-PEG gel were prepared by mixing tetra-PEG with thiol termini (tetra-PEG-SH) solution, maleimide termini (tetra-PEG-MA) solution, and bevacizumab or FAM-NHS labeled IgG. The gels were prepared with three different polymer concentrations of 1.5%, 5%, and 10%, then an in vitro release study performed to assess the sustained release ability of the drug-loaded tetra-PEG gels. High performance liquid chromatography (HPLC) was used to test the structural stability of the bevacizumab released from the tetra-PEG gel. The binding of bevacizumab to tetra-PEG-SH or MA was assessed using SDS-polyacrylamide gel electrophoresis (PAGE). The bioactivity of released bevacizumab was tested using KDR/NFAT-RE HEK293 cells. In addition, in vitro degradation and swelling studies were also performed. The in vitro release analysis showed that the release of bevacizumab was slower in the 5% and 10% tetra-PEG gels than that of 1.5% tetra-PEG gels. Similarly, the release of FAM-NHS-labeled IgG was slowest in the 1.5%, 5%, and 10% tetra-PEG gels, in that order. The 5% and 10% tetra-PEG gels released bevacizumab and FAM-NHS-labeled IgG over a period of 1-2 weeks. Both bevacizumab and FAM-NHS-labeled IgG were not fully released in 2 weeks. HPLC analysis showed that the retention time of the samples released from the bevacizumab-loaded tetra-PEG gel was similar to that of the bevacizumab standard. The SDS-PAGE analysis showed that bevacizumab binds to tetra-PEG-MA. The bioactivity assay test revealed no decrease in the bioactivity of the released bevacizumab. In vitro degradation and swelling studies revealed that 1.5%, 5%, and 10% tetra-PEG gels expanded by approximately 1.4-, 2-, and 3-fold, respectively. Based on the results of the release and swelling tests, 5% tetra-PEG gels are considered good candidates for controlled release systems for therapeutic antibodies such as bevacizumab. The binding of PEG to the therapeutic antibodies may reduce the availability of therapeutic antibodies that can be released.

Visual Functions Affecting Vision-Related Quality of Life Following Intravitreal Ranibizumab Therapy for Central Retinal Vein Occlusion.

Visual functions that affect vision-related quality of life (VR-QoL) before and after intravitreal injection of ranibizumab in patients with cystoid macular edema secondary to central retinal vein occlusion (CRVO-CME) are poorly understood. This multicenter, open-label, single-arm prospective study included 23 treatment-naïve patients with CRVO-CME. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS), severity of metamorphopsia (M-CHARTS), amount of aniseikonia (New Aniseikonia Test), and stereopsis (Titmus Stereo Test and TNO stereotest) were examined every month from before treatment to 12 months after treatment. For VR-QoL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was provided to the patients before treatment and at 3, 6, and 12 months after treatment. Stepwise multiple regression analysis revealed that the BCVA of the fellow eye was related to the VFQ-25 composite score before treatment, and that the BCVA of the fellow eye and TNO values were related to the VFQ-25 composite score 12 months after treatment. Changes in LCS were significantly correlated with changes in the VFQ-25 composite score. In patients with CRVO-CME, visual acuity of the fellow eye had the strongest impact on VR-QoL. The contrast sensitivity of the affected eye and stereopsis were also associated with VR-QoL.