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Abstract In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether the angle of incidence of the stimulus light from the fiber optic cable will affect the amplitudes and implicit times of the ERGs of zebrafish larvae. The larvae were positioned on their side with the right eye pointed upward. The light stimuli were delivered by a fiber optic cable from three directions of the larvae: frontal 0° (F0°), dorsal 30°(D30°), and ventral 30°(V30°). Photopic ERGs were recorded from 16 larvae at age 5–6 days post-fertilization. Our results showed that the mean amplitude of the b-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P = 0.014 and P = 0.019, respectively). In addition, the mean amplitude of the d-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P

Objectives: To develop a machine learning logistic regression algorithm that can classify patients with an idiopathic macular hole (IMH) into those with good or poor vison at 6 months after a vitrectomy. In addition, to determine its accuracy and the contribution of the preoperative OCT characteristics to the algorithm. Methods: This was a single-center, cohort study. The classifier was developed using preoperative clinical information and the optical coherence tomographic (OCT) findings of 43 eyes of 43 patients who had undergone a vitrectomy. The explanatory variables were selected using a filtering method based on statistical significance and variance inflation factor (VIF) values, and the objective variable was the best-corrected visual acuity (BCVA) at 6 months postoperation. The discrimination threshold of the BCVA was the 0.15 logarithm of the minimum angle of the resolution (logMAR) units. Results: The performance of the classifier was 0.92 for accuracy, 0.73 for recall, 0.60 for precision, 0.74 for F-score, and 0.84 for the area under the curve (AUC). In logistic regression, the standard regression coefficients were 0.28 for preoperative BCVA, 0.13 for outer nuclear layer defect length (ONL_DL), −0.21 for outer plexiform layer defect length (OPL_DL) − (ONL_DL), and −0.17 for (OPL_DL)/(ONL_DL). In the IMH form, a stenosis pattern with a narrowing from the OPL to the ONL of the MH had a significant effect on the postoperative BCVA at 6 months. Conclusions: Our results indicate that (OPL_DL) − (ONL_DL) had a similar contribution to preoperative visual acuity in predicting the postoperative visual acuity. This model had a strong performance, suggesting that the preoperative visual acuity and MH characteristics in the OCT images were crucial in forecasting the postoperative visual acuity in IMH patients. Thus, it can be used to classify MH patients into groups with good or poor postoperative visual acuity, and the classification was comparable to that of previous studies using deep learning.

Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF drugs were studied. All met the treatment suspension criteria and were followed for 5 years after the suspension of the anti-VEGF treatment. Patients with a recurrence within one year were placed in Group A, and patients with a recurrence between 1 and 5 years were placed in Group B. The rate and time of a recurrence were analyzed using the Kaplan–Meier method. We also examined whether there were differences in the baseline factors of age, sex, subtype, treatment period, and treatment interval between Groups A and B. Results: Twenty-five of 34 eyes (73.5%) had a recurrence within 5 years of stopping the anti-VEGF treatments. Thirteen (52.0%) of the 25 eyes had a recurrence within 1 year, 4 (16.0%) eyes between 1 and 2 years, 4 (16.0%) eyes between 2 and 3 years, 2 (8%) between 3 and 4 years, and 2 eyes (8%) between 4 and 5 years. The baseline factors were not significantly different between Groups A and B. Conclusions: The results showed that the recurrence rate was highest within one year after the suspension of the anti-VEGF treatments, with a number of recurrences one year after the suspension. Clinicians should remember that nAMD may recur several years after the suspension of anti-VEGF treatments.

BackgroundThe purpose of this study was to develop a model that can predict the postoperative visual acuity in eyes that had undergone vitrectomy for an epiretinal membrane (ERM). The Light Gradient Boosting Machine (LightGBM) was used to evaluate the accuracy of the prediction and the contribution of the explanatory variables. Two models were designed to predict the postoperative visual acuity in 67 ERM patients. Model 1 used the age, sex, affected eye, axial length, preoperative visual acuity, Govetto's classification stage, and OCT-derived vector information as features to predict the visual acuity at 1, 3, and 6 months postoperatively. Model 2 incorporated the early postoperative visual acuity as an additional variable to predict the visual acuity at 3, and 6 months postoperatively. LightGBM with 100 iterations of 5-fold cross-validation was used to tune the hyperparameters and train the model. This involved addressing multicollinearity and selecting the explanatory variables. The generalized performance of these models was evaluated using the root mean squared error (RMSE) in a 5-fold cross-validation, and the contributions of the explanatory variables were visualized using the average Shapley Additive exPlanations (SHAP) values.ResultsThe RMSEs for the predicted visual acuity of Model 1 were 0.14 ± 0.02 logMAR units at 1 month, 0.12 ± 0.03 logMAR units at 3 months, and 0.13 ± 0.04 logMAR units at 6 months. High SHAP values were observed for the preoperative visual acuity and the ectopic inner foveal layer (EIFL) area with significant and positive correlations across all models. Model 2 that incorporated the postoperative visual acuity was used to predict the visual acuity at 3 and 6 months, and it had superior accuracy with RMSEs of 0.10 ± 0.02 logMAR units at 3 months and 0.10 ± 0.04 logMAR units at 6 months. High SHAP values were observed for the postoperative visual acuity in Model 2.ConclusionPredicting the postoperative visual acuity in ERM patients is possible using the preoperative clinical data and OCT images with LightGBM. The contribution of the explanatory variables can be visualized using the SHAP values, and the accuracy of the prediction models improved when the postoperative visual acuity is included as an explanatory variable. Our data-driven machine learning models reveal that preoperative visual acuity and the size of the EIFL significantly influence postoperative visual acuity. Early intervention may be crucial for achieving favorable visual outcomes in eyes with an ERM.

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times.

Background and Objectives: Brolucizumab (IVBr) is a recently introduced anti-vascular endothelial growth factor (anti-VEGF) which has been found to be very effective in treating neovascular age-related macular degeneration (nAMD). We reported our findings in a case of nAMD that developed intraocular inflammation (IOI) after IVBr injections. Materials and Methods: A 79-year-old man was referred to our hospital complaining of reduced vision in both eyes of one-month’s duration. His decimal best-corrected visual acuity (BCVA) was 0.9 in the right eye and 1.0 in the left eye. He was diagnosed with nAMD in the left eye and was treated with intravitreal aflibercept (IVA). Despite the three-monthly IVA injections, the serous retinal pigment epithelial detachment (PED) and subretinal fluid (SRF) remained, and the VA gradually decreased to 0.1. Because of the patient being refractory to aflibercept treatment, we switched to 3-monthly IVBr injections. The BCVA gradually improved to 0.3 and optical coherence tomography (OCT) showed an absence of the serous PED and SRF. Three weeks after his third IVBr, he returned to our hospital with a complaint of reduced vision in his left eye that he first noted two weeks earlier. Our examination of the left eye showed signs of IOI mainly in the anterior chamber. The inflammation improved with topical steroids but the treatment of the IOI was delayed for two weeks. The patient was instructed that it was important to begin the treatment as soon as the symptoms of IOI developed. We then performed the Mini-Mental State Examination (MMSE), and his score indicated that he had cognitive impairment. Conclusions: We concluded that before beginning IVBr treatment in nAMD patients, a careful assessment must be made of the cognitive status of the patient.

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.

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.

Purpose: To determine whether the response to the initial anti-vascular endothelial growth factor (anti-VEGF) injection to treat diabetic macular edema (DME) is significantly correlated with the response to the third consecutive monthly injection of the same anti-VEGF agent. Methods: Seventy eyes with DME that were treated with an anti-VEGF agent (16 eyes with 1.25-mg bevacizumab, 35 eyes with 0.5-mg ranibizumab, and 19 eyes with 2.0-mg aflibercept) were studied. They were treated with three consecutive monthly injections of one of the three anti-VEGF agents. The best-corrected visual acuity (BCVA) in the logarithm of the minimum angle of resolution (logMAR units) and the central macular thickness (CMT) were measured at the baseline, 1 week after the initial injection, and 1 month after the third consecutive monthly injection. The changes of both values from the baseline 1 week after the initial injection (day 7) and 1 month after the third monthly injection were determined. The significance of the correlations between the BCVA and the CMT was determined. Results: The mean BCVA improved significantly for all three agents (0.38 ± 0.22 logMAR units at the baseline to 0.27 ± 0.25 logMAR units) after the three monthly injections (p < 0.05, repeated ANOVA). For all cases, a moderate but significant correlation was found between the BCVA at day 7 and 1 month after the third injection (r = 0.58, p < 0.01; Spearman’s rank correlation). No significant correlation was found for bevacizumab (r = 0.09, p = 0.73), moderate correlation was found for ranibizumab (r = 0.42, p < 0.05), and a strong correlation was found for aflibercept (r = 0.83, p < 0.001) between the BCVA at day 7 and at 1 month after the third injection. The mean CMT improved significantly for all three agents (481.9 ± 96.3 μm at the baseline to 364.1 ± 116.0 μm after the three monthly injections, p < 0.05), and a moderate correlation was found for the three agents between CMT at day 7 to that at one month after the third anti-VEGF injection (r = 0.54, p < 0.01). A moderate correlation was found for all three agents between CMT at day 7 to that at one month after the third anti-VEGF injection (r = 0.68 for bevacizumab, r = 0.41 for ranibizumab and r = 0.53 for aflibercept, p < 0.05). Conclusions: The significant correlations between the results on day 7 to that one month after the third anti-VEGF treatment for DME indicates that the long-term effects of anti-VEGF therapy can be predicted by the short-term response. In addition, the results indicate that there may be differences in the effectiveness between the three anti-VEGF agents.

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.

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-naïve 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 ± 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. No significant differences were detected in the baseline demographics. At 24 months, 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 = 1.29 × 10−9). 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 = 3.55 × 10−9). No significant differences were detected in the improvements of BCVA, CRT in both groups, and the total injection numbers for 24 months (11.0 ± 1.2 for the IVA group and 12.0 ± 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.

Purpose: To determine the mechanism for the development of segmental granular lesions along the retinal vessels in eyes with acute retinal necrosis. Method: This was a retrospective analysis of the medical records of three eyes of three patients who were diagnosed with acute retinal necrosis that had atypical segmental granular lesions aligned along the retinal vessels. Results: The segmental granular lesions were present on the retinal arteries and veins throughout the retina. Optical coherence tomography showed that the granular lesions protruded into the vitreous cavity. Histopathologic examinations confirmed that the lesions were made up of lymphocytes. Conclusion: We suggest that the granular lesions were formed by a mechanism similar to that of HTLV-1-associated uveitis. We also found that the granular lesions disappeared soon after vitrectomy. [ABSTRACT FROM AUTHOR]