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Epiretinal membrane (ERM) foveoschisis is a recently proposed clinical entity. The purpose of this study was to compare the clinical characteristics and surgical outcomes of eyes with ERM foveoschisis to those of typical ERM. The medical records of all patients with ERM-related disorders examined between 2011 and 2020 were reviewed. ERM foveoschisis was defined by the clinical criteria proposed by an international panel of experts on ERMs. The background factors, clinical characteristics, and surgical outcomes of ERM foveoschisis were compared to those of typical ERM. Forty eyes with ERM foveoschisis were compared to 333 eyes with typical ERM. The percentage of women was significantly higher in the ERM foveoschisis group (92.5%) than in the typical ERM group (48.9%, p < 0.001). The central macular thickness (CMT) was significantly thinner in the ERM foveoschisis group (340 ± 110 μm) than in the typical ERM groups (476 ± 111 μm, p < 0.01). The degree of improvement in the best-corrected visual acuity (BCVA) three months after the surgery did not differ between the two groups (p = 0.59). These results suggest that the ERM foveoschisis is more likely to occur in women and that the prognosis after surgery is comparable to typical ERM.

Shin Asami, Masahiko Sugimoto, Hideyuki Tsukitome, Kumiko Kato, Hisashi Matsubara, Mineo Kondo Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, JapanCorrespondence: Masahiko Sugimoto, Department of Ophthalmology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan, Tel +81-59-231-5027, Fax +81-59-231-3036, Email sugmochi@clin.medic.mie-u.ac.jpPurpose: To compare the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) agents in eyes with macular edema associated with branch retinal vein occlusion (BRVO-ME) with glaucoma to those without glaucoma.Patients and Methods: This retrospective study was conducted using the medical records of Mie University Hospital from 2013 to 2017. Patients were recruited if they had received anti-VEGF agents for BRVO-ME treatment and included 30 patients (30 eyes) without glaucoma (G[-] group) and 27 patients (27 eyes) with glaucoma (G[+] group). The central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at 3 months after a single injection of anti-VEGF agents were compared between the two groups.Results: Before treatment, the mean±standard deviation of the CRT was 514.2± 117.3 μm for the G[-] group, which was not significantly different from that for the G[+] group (533.4± 171.4 μm). The CRT in the G[-] and G[+] groups significantly reduced to 321.1± 114.6 μm and 347.8± 134.7 μm, respectively, at 1 month after the injection and to 360.4± 159.5 μm and 352.4± 151.9 μm, respectively, at 3 months after the injection (P< 0.01 for each group). The difference in the degree of CRT reduction between the two groups was not significant. Before treatment, the BCVA was 0.42± 0.32 logMAR units in the G[-] group and 0.57± 0.33 logMAR units in the G[+] group, showing no significant difference. The BCVA in the G[-] and G[+] groups improved significantly to 0.27± 0.26 logMAR units and 0.34± 0.42 logMAR units, respectively, at 1 month, and to 0.18± 0.20 logMAR units and 0.39± 0.34 logMAR units, respectively, at 3 months (P< 0.01). The BCVA in the G[-] group was significantly better than that in the G[+] group at 3 months (P=0.02).Conclusion: The therapeutic response of anti-VEGF agents for BRVO-ME is affected by the presence of glaucoma.Keywords: anti-vascular endothelial growth factor treatment, branch retinal vein occlusion, glaucoma, macular edema

Purpose: To determine whether atrophy of the retinal pigment epithelium (RPE) in eyes with neovascular age-related macular degeneration (nAMD), which meets the criteria for the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatment, is associated with anti-VEGF treatments. Methods: Twelve eyes of 12 patients with nAMD who began anti-VEGF treatment and were followed for 1 year after meeting the criteria for the suspension of anti-VEGF were studied. Six eyes of six patients were placed in the continuation group, and six eyes of six patients were placed in the suspension group. The RPE atrophic area at the time of the last anti-VEGF treatment was set as the baseline size and that at 12 months after the baseline (Month 12) was taken as the final size. A comparison of the expansion rate of RPE atrophy between the two groups was made by the square-root transformed differences. Results: The expansion rate of atrophy was 0.55 (0.43, 0.72) mm/year in the continuation group and 0.33 (0.15, 0.41) mm/year in the suspension group. This difference was not significant. (p = 0.29). Conclusions: Suspension of anti-VEGF treatments in eyes with nAMD does not alter the expansion rate of RPE atrophy.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Purpose To investigate the outcomes of a suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments in the eyes with neovascular age-related macular degeneration (nAMD). Methods This was a retrospective study that examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity (BCVA), central subfield thickness (CST), number of visits, and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments. Results In 34 eyes of 34 patients, 17 eyes (50.0%) had a recurrence during the 24-month follow-up period. The median time of a recurrence was 10 months. The BCVA was maintained for 24 months after the suspension regardless of the development of any recurrences. In 41.7% of the eyes that resumed treatment, the duration of exudation suppression by the anti-VEGF therapy was shorter than 12 weeks during the 12 months after restarting the anti-VEGF treatments. There was a significant increase in the number of visits during the first year after beginning the suspension versus during the 1 year before the suspension (non-recurrence group; P = 0.007, recurrence group; P = 0.001). Conclusion Although one-half of the eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, the BCVA was maintained after a resumption of the anti-VEGF treatments. However, the number of hospital visits increases regardless of the recurrences and the lesion stability is altered by the anti-VEGF suspension. Clinicians should explain both the advantages and disadvantages of anti-VEGF suspension to nAMD patients.

To identify the eyes with macular edema (ME) due to a branch retinal vein occlusion (BRVO) that have good visual acuity during the continuous anti-vascular endothelial growth factor (anti-VEGF) treatment based on the patients’ clinical information and optical coherence tomography (OCT) images by using machine learning. Sixty-six eyes of 66 patients received 1 anti-VEGF injection followed by repeated injections in the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the 1-year experimental period. Handcraft features were defined from the OCT images at the time of the first resolution of the ME. Variables with a significant difference between the groups were used as explanatory variables. A classifier was created with handcrafted features based on a support vector machine (SVM) that adjusted parameters for increasing maximal precision. The age, best-corrected visual acuity (BCVA) at the baseline, BCVA at the first resolution of the ME, integrity and reflectivity of the external limiting membrane (ELM), the ellipsoid zone (EZ), and area of the outer segments of the photoreceptors were selected as explanatory variables. The classification performance was 0.806 for accuracy, 0.768 for precision, 0.772 for recall, and 0.752 for the F-measure. The use of the SVM of the patient’s clinical information and OCT images can be helpful for determining the prognosis of the BCVA during continued pro re nata anti-VEGF treatment in eyes with ME associated with BRVO.

Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.

Purpose: To assess the blood flow and vascular visibility of irises in relation to pigmentation and pupil size, using an anterior segment optical coherence tomography angiography (OCTA). Materials and methods: This is a cross-sectional study. OCTA images were acquired in the nasal and temporal quadrants from a cohort of 30 healthy subjects in photopic (miosis) and scotopic (mydriasis) conditions. Patients were divided according to iris color (less pigmented: group L vs more pigmented: group D). Vascular parameters (vessel density (VD), vessel length density (VLD), fractal dimension (FD)) were applied and compared among groups L and D, location and different pupil status. A novel vascular index called Luminance Index (LI) was developed and applied in order to quantify vascular flow and evaluate its variation in photopic and scotopic conditions. Multivariable analyses were performed to evaluate possible predictors of VD and LI. Results: No differences were found for all vascular measurements (VD, VDL, FD, LI) between nasal and temporal quadrants. All vascular measurements were higher in group L than in group D ( p Conclusions: Pigmentation still remains a major issue for vascular visibility. Quantitative and qualitative vascular changes follow pupil size variation. LI could be a new surrogate to quantify blood flow.

This study’s goal is to determine the accuracy of a linear classifier that predicts the prognosis of patients with macular edema (ME) due to a branch retinal vein occlusion during the maintenance phase of antivascular endothelial growth factor (anti-VEGF) therapy. The classifier was created using the clinical information and optical coherence tomographic (OCT) findings obtained up to the time of the first resolution of ME. In total, 66 eyes of 66 patients received an initial intravitreal injection of anti-VEGF followed by repeated injections with the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the PRN phase. The mean AUC of the classifier was 0.93, and the coefficients of the explanatory variables were: best-corrected visual acuity (BCVA) at baseline was 0.66, BCVA at first resolution of ME was 0.51, age was 0.21, the average brightness of the ellipsoid zone (EZ) was −0.12, the intactness of the external limiting membrane (ELM) was −0.14, the average brightness of the ELM was −0.17, the brightness value of EZ was −0.17, the area of the outer segments of the photoreceptors was −0.20, and the intactness of the EZ was −0.24. This algorithm predicted the prognosis over time for individual patients during the PRN phase.

To determine the characteristics and cause of the increase in the amplitude of flicker electroretinography (ERG) after cataract surgery.Prospective, observational clinical study.Thirty patients who underwent cataract surgery.Flicker ERGs were recorded with the RETeval system without mydriasis. The central macular thickness (CMT) was measured by OCT and the aqueous flare value (AFV) by laser flare-cell photometry. These examinations were performed before surgery and 1 day, 1 week, 1 month, 2 months, and 3 months after surgery. Linear regression analysis through the origin was used to compare the correlations between the relative changes in flicker ERG amplitudes and the changes in the CMT and AFV at different times after the surgery.The amplitude of flicker ERGs, CMT, and AFV.The mean amplitude of flicker ERGs increased significantly by 31% at 1 week after surgery (These results suggest that the increase in the amplitude of flicker ERGs after cataract surgery is a transient phenomenon that has a peak at 1 week after surgery. The increase of flicker ERG amplitude was associated with measures that are frequently used to evaluate postoperative inflammation.Proprietary or commercial disclosure may be found after the references.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is essential for the treatment of macular diseases such as wet age-related macular degeneration and macular edema. Although continued treatment is needed to maintain good vision, some patients cannot continue such injections for various reasons, including specific phobias. Here, we report a case of a patient with a specific phobia of intravitreal injections who could resume treatment after undergoing combined drug and cognitive-behavioral therapy (CBT). A 74-year-old Japanese man diagnosed with retinal angiomatous proliferation by fluorescein angiography and indocyanine green angiography was treated with intravitreal anti-VEGF injection. However, at 8 months after the first treatment, he became difficult to treat because of a phobia of injections. He was treated with photodynamic therapy, but his macular edema did not improve. After a psychiatric consultation, he was diagnosed with a specific phobia of intravitreal injections. Combined drug and CBT enabled him to resume receiving intravitreal injections. This case demonstrates that a specific phobia of intravitreal injections may benefit from combined drug and CBT. In this regard, some patients with high anxiety and fear of intravitreal injections should be referred to a psychiatrist at an early stage.

To investigate potential clinical and multimodal imaging factors in central serous chorioretinopathy (CSC) recurrence.The study was performed at nine Japanese medical institutions for patients who had experienced an active CSC episode. Demographic data and medical history were reviewed retrospectively. Significant differences in chronic manifestation, leakage site, leakage point number, leakage intensity, choroidal hyperpermeability, central retinal thickness (CRT) and subfoveal choroidal thickness were analysed between the recurrence and non-recurrence groups.In total, 538 eyes (538 patients) diagnosed with CSC (402 men, 136 women; mean age: 53.4 ± 11.9 years) were enrolled. Among them, 253 eyes (47.0%) developed ≥1 recurrence (follow-up: 15.9 ± 13.5 months, range 3-86 months). Univariate and multivariate analyses indicated that a history of corticosteroid use (odds ratio [OR], 5.52; 95% confidence interval [CI], 1.39-21.92; p = 0.015), bilateral disease (OR, 3.94; 95% CI, 1.47-10.6; p = 0.007), chronic manifestations (OR, 7.12; 95% CI, 2.93-17.28; p 0.001), non-intense fluorescein leakage (OR, 3.34; 95% CI, 1.44-7.75; p = 0.005) and initial CRT (OR, 0.997; 95% CI, 0.993-0.999; p = 0.049) were significantly associated with CSC recurrence. Receiver operating characteristic curves were created, and the area under the curve for the multivariate logistic regression model of these five factors was 0.814.Patients with CSC who received corticosteroids and had bilateral disease, chronic manifestation, non-intense fluorescein leakage on fluorescein angiography or a relatively thinner CRT should be closely monitored to identify whether they are at high risk of recurrence.

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.

Background A new handheld electroretinographic (ERG) recording system can record ERGs without mydriasis. However, this RETeval system cannot record ERGs from both eyes simultaneously. Thus, the purpose of this study was to determine whether the sequence of the ERG recordings will alter the results. Methods We studied 30 eyes of 30 healthy subjects. The flicker ERGs were recorded with the RETeval system without mydriasis and were elicited by 8, 16 and 32 photopic Td‐s. The flicker ERGs were recorded at two sessions. Session 1, the ERGs were recorded from the right eye and then the left eye, and Session 2, ERGs were recorded from the left eye then the right eye. We compared the implicit times, amplitudes and pupil diameters of the right eye between these two sessions. Results The implicit time of the flicker ERGs was significantly shorter (p

This is the first reported case of a successful resolution of cystic-like foveal cavities in eyes with X-linked juvenile retinoschisis (XLRS) treated with topical ripasudil hydrochloride hydrate, a Rho-associated coiled/coil-containing protein kinase (ROCK) inhibitor. A chart review was performed on 1 patient to collect all relevant clinical information and the optical coherence tomographic (OCT) images. A healthy 18-year-old young man presented with bilateral visual disturbances. The patient was diagnosed with XLRS from the spoke-wheel pattern around the macula, negative electroretinograms, and retinoschisis with cystic-like foveal cavities in the OCT images. Significant reductions of the retinoschisis and cystic-like cavities were observed after treatment with topical ripasudil. This is the first case of XLRS that had a resolution of cystic-like foveal cavities after topical ripasudil, a ROCK inhibitor. Since many XLRS patients have a worsening of their visual acuities due to the progressive nature of retinoschisis and cystic-like foveal cavities, topical ripasudil offers a potential treatment option.

The foveal bulge (FB) results from a lengthening of the outer segments of the photoreceptors which then makes the central fovea arcuate in shape. The purpose of this study was to evaluate the morphological features and locations of the FB relative to the foveal pit (FP) in a single B-scan image. One hundred and forty-seven eyes of 147 healthy volunteers were studied. Horizontal and vertical B-scan optical coherence tomographic (OCT) images through the fovea were recorded by an ultrahigh-resolution spectral domain OCT (UHR-SD-OCT) instrument (Bi-μ, KOWA, Japan). The vertex of the FB and the center of the FP were identified with the ImageJ software. The distance between the FB and FP and the height of the FB were measured. In the horizontal images, the vertex of the FB was on the nasal side of the center of the FP in 97 eyes (66%), on the temporal side in 42 eyes (29%), and the same position in 8 eyes (5%). In the vertical images, the vertex of the FB was superior to the center of the FP in 82 eyes (55%), inferior to the center of the FP in 45 eyes (31%), and the same position in 20 eyes (14%). The mean distance (± SD) between the FB and the FP was + 16.8 ± 30.1 μm in the horizontal images and + 8.27 ± 28.0 μm in the vertical images. The mean height (± SD) of the FB was 77.0 ± 4.78 μm in the horizontal images and 77.9 ± 5.05 μm in the vertical images. The height of the FB in the horizontal images was significantly correlated with refractive error in the multiple regression analysis (P = 0.041). These results indicate that the vertex of the FB was not aligned with the center of the FP in the majority of the eyes of normal Japanese individuals in a single B-scan image. Analysis showed that eyes with less severe myopia had the higher height of the FB. This must be considered when interpreting the location of the vertex of the FB and the center of the FP in clinical situations.

To report abnormal full-field electroretinograms (ERGs) in a patient with cystoid macular edema (CME) induced by systemic paclitaxel. This is an observational case report. Full-field ERGs were recorded to evaluate the retinal function using the RETeval system and conventional ERGs using contact lens electrodes with built-in white light-emitting diodes. Optical coherence tomography (OCT) was also used to assess the retinal morphology. A 70-year-old man, who was diagnosed with gastric cancer, had undergone gastrectomy. Subsequently, systemic paclitaxel was administered once a week as an adjuvant therapy. After the tenth course of paclitaxel, he experienced blurred vision in both eyes and visited our department of ophthalmology. OCT revealed the presence of CME in both eyes, and the RETeval flicker ERGs showed a marked reduction in the amplitudes and a prolongation of the implicit times in both eyes. Conventional ERGs showed that the amplitudes of the oscillatory potentials (OPs) were also severely attenuated. The abnormal OCT findings and reduced visual acuity recovered to normal at 1 and 2 months, respectively, after the discontinuation of paclitaxel. However, the flicker ERGs did not recover to normal values until 4 months after the discontinuation of paclitaxel. These results suggest that the ERGs can be used to monitor the changes in the overall retinal function in patients receiving paclitaxel.

Purpose Wearing a sports mouthguard is not only recommended in collision sports, such as American football, boxing, and rugby football, but also in low-contact sports, such as basketball, handball, and soccer. It is recommended to remove oral prosthetic devices while playing sports to avoid the risk of fracturing the device. However, players with maxillectomy must wear obturator-type prosthetic devices for speech, breathing, and deglutition even while playing sports. Therefore, there is a need for an oral appliance to prevent dental injury while playing sports without the risk of fracturing the device for players who have undergone maxillectomy.In this case, we fabricated and proposed overlay-type and obturator-type customized sports mouthguards for a patient who had undergone maxillectomy and assessments of satisfaction, speech intelligibility, nasopharyngeal closure function, and swallowing function while playing soccer. Results The patient was only satisfied with the obturator-type mouthguard, and the results of the speech intelligibility, nasopharyngeal closure function, and swallowing tests using the obturator-type mouthguard showed no differences compared to those associated with the previously used prosthetic device. Conclusions This case may help highlight the importance of providing obturator-type mouthguards for players who have undergone maxillectomy to prevent dental injury and physical and mental discomfort.

Background: To compare the effectiveness of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) performed with the treat-and-extend (TAE) regimen on eyes with diabetic macular edema (DME). Patients and methods: This is a retrospective study of 125 eyes of 125 treatment-na&iuml, ve DME patients who received anti-VEGF injections at three consecutive monthly intervals as the loading phase. The changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), diabetic retinopathy severity scale (DRSS), and total injection numbers were compared between the two anti-VEGF agents. Results: Among 125 eyes, 26 eyes completed the treatment with the TAE regimen for 24 months (20.8%). Thirteen eyes of 13 patients (mean age, 70.9 &plusmn, 6.0 years) received intravitreal injections of 0.5 mg ranibizumab, and 13 eyes of 13 patients (65.9 &plusmn, 8.6 years) received 2 mg aflibercept. No significant differences were detected in the baseline demographics. At 24 months, BCVA was significantly improved in both groups, from 0.31 &plusmn, 0.19 to 0.10 &plusmn, 0.12 logMAR units for IVR and 0.41 &plusmn, 0.19 to 0.16 &plusmn, 0.28 logMAR units for IVA (p = 1.29 &times, 10&minus, 9). CRT was significantly reduced in both groups, 440.9 &plusmn, 69.3 to 307.5 &plusmn, 66.4 &mu, m for IVR and 473.9 &plusmn, 71.5 to 317.8 &plusmn, 71.2 &mu, m for IVA (p = 3.55 &times, 9). No significant differences were detected in the improvements of BCVA, CRT in both groups, and the total injection numbers for 24 months (11.0 &plusmn, 1.2 for the IVA group and 12.0 &plusmn, 1.0 the IVR group). DRSS was significantly improved in both groups (p = 0.0004 for IVR and p = 0.009 for IVA). Conclusion: No significant differences were detected in the improvements of BCVA or CRT and injection numbers between the IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective, but only 20.8% of patients completed 24 months of continuous treatment with the TAE regimen. Synopsis: There are no significant differences regarding effectiveness between the IVR and IVA groups treated with the TAE regimen for DME eyes.

Background Acquired color anomalies caused by cerebral trauma are classified as either achromatopsias or dyschromatopsias (Zeki, Brain 113:1721–1777, 1990). The three main brain regions stimulated by color are V1, the lingual gyrus, which was designated as human V4 (hV4), and the fusiform gyrus, designated as V4α. (Zeki, Brain 113:1721–1777, 1990). An acquired cerebral color anomaly is often accompanied by visual field loss (hemi- and quadrantanopia), facial agnosia, prosopagnosia, visual agnosia, and anosognosia depending on the underlying pathology (Bartels and Zeki, Eur J Neurosci 12:172–193, 2000), (Meadows, Brain 97:615–632, 1974), (Pearman et al., Ann Neurol 5:253–261, 1979). The purpose of this study was to determine the characteristics of a patient who developed dyschromatopsia following a traumatic injury to her brain. Case presentation The patient was a 24-year-old woman who had a contusion to her right anterior temporal lobe. After the injury, she noticed color distortion and that blue objects appeared green in the left half of the visual field. Although conventional color vision tests did not detect any color vision abnormalities, short wavelength automated perimetry (SWAP) showed a decrease in sensitivity consistent with a left hemi-dyschromatopsia. Magnetic resonance imaging (MRI) detected abnormalities in the right fusiform gyrus, a part of the anterior temporal lobe. At follow-up 14 months later, subjective symptoms had disappeared, but the SWAP abnormalities persisted and a thinning of the sectorial ganglion cell complex (GCC) was detected. Conclusion The results indicate that although the subjective symptoms resolved early, a reduced sensitivity of SWAP remained and the optical coherence tomography (OCT) showed GCC thinning. We conclude that local abnormalities in the anterior section of fusiform gyrus can cause mild cerebral dyschromatopsia without other symptoms. These findings indicate that it is important to listen to the symptoms of the patient and perform appropriate tests including the SWAP and OCT at the early stage to objectively prove the presence of acquired cerebral color anomaly.

To report our findings in a case of lens fragment-induced uveitis associated with supernormal flicker electroretinograms (ERGs) twenty months after the cataract surgery. This is an observational case report. Full-field flicker ERGs were recorded with the RETeval system. Optical coherence tomography (OCT) and slit-lamp biomicroscopy were used to assess the uveitis during the follow-up period. A 70-year-old man, who had undergone cataract surgery 20 months earlier, visited our hospital with a complaint of decreased vision in his right eye. Slit-lamp biomicroscopy revealed corneal edema and a lens fragment was detected in the inferior part of the anterior chamber. OCT showed cystoid macular edema, and flicker ERGs showed a marked increase in the amplitude and a delay in the implicit time in the right eye. These abnormalities of the flicker ERGs improved gradually after the removal of lens fragment and application of topical anti-inflammatory medications. Our case of lens-induced uveitis had supernormal flicker ERG amplitudes. Clinicians should be aware that eyes with uveitis can have larger-than-normal ERG amplitudes.

A new clinical ultrahigh-resolution spectral domain optical coherence tomography (UHR-SD-OCT) system using an original averaging technique named “A-scan matching algorithm” was developed. The aim of this study was to determine whether our new UHR-SD-OCT system can obtain clearer sectional images of the retina than conventional standard resolution SD-OCT systems (SR-SD-OCT). We recorded horizontal B-scan images of 42 normal eyes using our new UHR-SD-OCT device (Bi-μ, Kowa) and a conventional SR-SD-OCT (Spectralis, Heidelberg). To evaluate the clarity of the interdigitation zone (IZ) subjectively, the integrity of IZ was divided into three types by two raters. To evaluate the clarity of the IZ objectively, a peak height score (PHS) was calculated at five different points of the macula using the longitudinal reflectivity profile. The mean (± SD) of the subjective visibility score of the IZ in the UHR-SD-OCT images was 2.64 ± 0.54 which was significantly higher than the 2.46 ± 0.46 in the SR-SD-OCT images (P = 0.02). The PHS was also significantly higher for the UHR-SD-OCT than for the SR-SD-OCT images at all five locations (all P

Focal choroidal excavation (FCE) is described as an excavated lesion of the choroid that can be detected by optical coherence tomography (OCT). While the exact pathogenesis of FCE remains unclear, it has been proposed in some cases that there is an association with the inflammation in the outer retina. We present a case of FCE development that was detected by spectral domain OCT (SD-OCT) and found to be associated with multiple evanescent white dot syndrome (MEWDS). A 40-year-old Japanese woman was diagnosed with MEWDS based on multiple white dots observed from the posterior pole to the midperiphery, along with yellow granularity in the fovea. SD-OCT revealed separation between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) and discontinuations of the ellipsoid zone, RPE, and BM. At 4 weeks after onset, several of the white dots disappeared, the yellow granularity in the fovea became small, and we detected nonconforming choroidal excavation under the central fovea. The choroidal excavation gradually deepened and changed to a conforming pattern. These findings suggest that the degree of the impairment caused by inflammation and the plasticity of the BM and RPE complex may be associated with different types of acquired FCE.

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.

Purpose The zebrafish is an established animal model commonly used in biological, neuroscience, and genetic research. We have developed a new light stimulating system using white light-emitting diodes (LEDs) to elicit ERGs from zebrafish larvae. The purpose of this study was to record full-field ERGs and to evaluate the inter-trial reliability of the ERGs recorded with our system from zebrafish larvae. Methods The stimulating device used white LEDs that were attached to a stereomicroscope, and the location of the recording electrode on the cornea could be monitored while the eye was being stimulated. Full-field scotopic and photopic ERGs were recorded from larvae at the age of 5–7 days post-fertilization (dpf). Intensity–response curves were constructed from the ERGs. Inter-trial reliability of the ERGs recorded by our system was evaluated. Results This stimulating system could be used for efficient and reliable ERG recordings from 5–7 dpf larvae. The amplitudes, implicit times, and the waveforms of the scotopic and photopic ERGs were similar to those reported in earlier studies. Inter-trial reliability of the amplitudes of the photopic ERG b-waves was excellent with an intra-class correlation coefficient of 0.98. Conclusion We conclude that this new light stimulation system using white LEDs attached to a stereomicroscope will be helpful in recording reliable ERGs from zebrafish larvae.

Background To compare the effectiveness of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) performed with the Treat-and-Extend (TAE) regimen on eyes with diabetic macular edema (DME).Patients and methods This was a retrospective study of 125 eyes of 125 treatment naïve DME patients who received anti-VEGF injections at 3 consecutive monthly intervals as the loading phase. Of these 125 eyes, 26 eyes completed the treatment with the TAE regimen for at least 24 months. Among the 26 eyes, 13 eyes of 13 patients (mean age, 70.9±6.0 years) received intravitreal injections of 0.5 mg ranibizumab and 13 eyes of 13 patients (65.9±8.6 years) received 2 mg aflibercept. The changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), diabetic retinopathy severity (DRS), and total injection numbers were compared between the two anti-VEGF agents.Results No significant differences were detected in the baseline demographics. At 24 months, the BCVA was significantly improved in both groups; from 0.31±0.19 to 0.10±0.12 logMAR units for IVR and 0.41±0.19 to 0.16±0.28 logMAR units for IVA ( P=1.29x10 -9 ). The CRT was significantly reduced in both groups; 440.9±69.3 to 307.5±66.4 μm for IVR and 473.9±71.5 to 317.8±71.2 μm for IVA ( P=3.55x10 -9 ). No significant differences were detected in the improvements of the BCVA and the CRT in both groups, and the total injection numbers were significant fewer for the IVA group (11.0±1.2) than the IVR group (12.0±1.0). The DRS was significantly improved in both groups ( P =0.0004 for IVR and P =0.009 for IVA).Conclusion No significant differences were detected in the improvements of the BCVA or CRT and injection numbers between IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective.

Purpose. To compare the effective fields of the Optos 200Tx® and Clarus 500™, two ultra-widefield ophthalmoscopes, based on their ability to image branches of retinal vessel in the four retinal quadrants. Methods. Ninety retinal images from 90 patients with various eye diseases were studied. All patients had undergone 200° retinal imaging to obtain a single image of Optos (O) and the montage of two images of the Clarus (C). The highest number of traceable vessel branches in the four retinal quadrants was determined by two masked raters. An image was classified as “O > C” when the number of identifiable branch was greater in the Optos than the Clarus, as “O = C” when the number was equal and as “O Results. The appearance probability of “O > C” was significantly higher at the upper temporal quadrant than “O p<0.01 for both raters). In contrast, the appearance probability of “O C” (p<0.01 for both raters). There were no significant differences in the appearance probability between “O > C” and “O p>0.50 for both raters). Conclusions. These results demonstrate that the effective field of views was different between the two devices at different retina quadrants. Further studies are needed to clarify possible factors such as artifacts by the eyelashes, differences in the depth of focus, motion of the device, and different locations of the images on the effective field of views.

To determine whether an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in eyes with diabetic macular edema (DME) affects the vascular infarction-related molecules (VIRMs). Nineteen eyes with DME were treated with 0.5 mg of intravitreal ranibizumab (IVR), and 22 eyes with DME were treated with 2 mg of intravitreal aflibercept (IVA). Blood was collected before, 1 week and 1 month after the injections. Aqueous humor was collected before and 1 month after the injections. The concentration of the VIRMs (cardiac myoglobin, cardiac troponin, intercellular adhesion molecule, monocyte chemotactic protein-1, matrix metalloproteinase-8, placental growth factor [PlGF], tenascin-C, tissue inhibitor of metalloproteinase-1, thrombospondin-2, vascular cell adhesion molecule-1, and VEGF) were determined by the multiplex assay. After the single injection of both types of anti-VEGF agents, the concentration of aqueous VEGF decreased significantly (P P

Purpose To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME). Design Interventional, prospective study. Participants Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections. Methods Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined. Main Outcome Measures The mean number of microaneurysms and NPA evaluated as the ISI. Results At baseline, the mean CRT was 485.7±90.6 μm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 μm (P = 0.1 × 10–5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P = 0.3 × 10–5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P = 0.3 × 10–5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r = 0.56; P = 0.004) and after treatment (r = 0.53; P = 0.006). A significant correlation was found between CRT and ISI at baseline (r = –0.39; P = 0.03) but not after treatment (r = –0.06; P = 0.79). Conclusions The reduction in the number of microaneurysms was correlated with reduction in CRT.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.