Volume-rendering three-dimensional image analysis of macular neovascularization in age-related macular degeneration.

BACKGROUND: To visualize and investigate the three-dimensional (3D) images of macular neovascularization (MNV) in eyes with neovascular age-related macular degeneration using optical coherence tomography angiography (OCTA) according to the treatment response to intravitreal aflibercept injection (IVI). METHODS: OCTA images at baseline and 12 weeks (after three loading IVIs) were retrospectively reconstructed as 3D images for patients with type 1 and 2 MNV treated with the "pro-re-nata" regimen. The fluid-free and persistent fluid groups were divided according to the presence of subretinal and intraretinal fluid at 12 weeks after treatment. Using reconstructed 3D images of MNV, the volume, average volume per slice, and z-axis of the volumetric structure were evaluated. RESULTS: Twenty-three and nine were classified into the fluid-free and persistent fluid groups, respectively. The MNV volume decreased significantly from baseline to 12 weeks in the fluid-free group (p = 0.005), not in the persistent fluid group (p = 0.250). The average volume of MNV per slice at 12 weeks correlated with the persistent fluid group in both the univariate and multivariate analyses (p = 0.034, p = 0.039, Exp [B] = 14.005). CONCLUSIONS: This study may provide a perspective on vascular volumetric changes of MNV according to treatment response.

Anatomical changes in idiopathic epiretinal membrane at 2-year follow-up assessed using spectral domain optical coherence tomography and optical coherence tomographic angiography.

PURPOSE: To evaluate anatomical changes in the low-stage partial attachment-type idiopathic epiretinal membrane (iERM) over 2 years. METHODS: Data from patients with low-stage partial attachment-type iERM (stage 2) were analyzed. The main outcome measures were anatomical changes, including changes in the foveal avascular zone (FAZ) area, vessel density (VD) in the vascular plexus, and thickness of retinal sublayers during the follow-up period. RESULTS: Thirty patients (mean age: 68±12 years) were included in the study. The FAZ area on the superficial vascular plexus (SVP) significantly decreased from baseline (0.12±0.08 mm2) to month 24 (0.10±0.08 mm2, p=0.024). However, the FAZ area on the deep vascular plexus (DVP) did not significantly decrease from baseline (0.15±0.13 mm2) to month 24 (0.14±0.14 mm2, p=0.099). VDs on both the SVP and DVP did not show significant change from baseline (29.51±8.14% vs. 28.35±5.63%) to month 24 (29.79±9.77%, p=0.564 vs. 28.17±5.75%, p=0.417). Parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness decreased from baseline (108.77±13.61 µm) to month 24 (103.03±15.54 µm, p=0.004). The central total retinal layer thickness did not significantly change from baseline (396.07±64.86 µm) to month 24 (392.04±72.72 µm, p=0.570). CONCLUSION: Even in low-stage ERM, inner retinal changes, including GCIPL thickness, occurred during follow-up periods, which might be owing to degenerative changes or centrifugal movement.

Clinical Factors, Treatment Selection, and Outcomes in Postcataract Fungal Endophthalmitis from Contaminated Viscoelastics.

PURPOSE: To investigate the factors associated with treatment outcomes of postcataract surgery fungal endophthalmitis outbreaks related to contaminated viscoelastics. DESIGN: Retrospective analysis of clinical data from multiple institutions. SUBJECTS: This study included 228 eyes of 210 patients who were diagnosed with postcataract surgery fungal endophthalmitis related to the use of viscoelastic material (Unial, Unimed Pharmaceutical Inc); they were followed up for 6 months after the diagnosis. METHODS: Clinical features and causative species were identified and treatment outcomes were analyzed in patients who underwent 6 months of follow-up. Propensity score matching was conducted to elucidate the impact of vitrectomy timing and intraocular lens (IOL) removal on treatment outcomes. MAIN OUTCOME MEASURES: Clinical factors and selection of treatment modalities associated with treatment outcomes at 6 months. RESULTS: Baseline visual acuity (P < 0.01), age (P = 0.05), and the presence of corneal edema (P < 0.01) were closely associated with poor best-corrected visual acuity (BCVA) at 6 months. Patients who underwent immediate vitrectomy after diagnosis showed significantly better BCVA at 6 months (mean logarithm of minimum angle of resolution 0.26 ± 0.43 vs. 0.52 ± 0.52, P = 0.03) and greater degree of visual improvement (mean -0.17 ± 0.37 improvement vs. 0.10 ± 0.57 deterioration, P = 0.03) than those who underwent deferred vitrectomy. Patients who underwent IOL removal during vitrectomy required a lower number of intravitreal antifungal agent injections (mean 8.9 ± 9.1 vs. 16.7 ± 12.2, P < 0.01) and showed a lower incidence of repeated vitrectomy (20% vs. 82%, P < 0.01) than in those without IOL removal. CONCLUSIONS: In postcataract fungal endophthalmitis, prompt vitrectomy at the time of diagnosis resulted in better treatment outcomes, and IOL removal reduced the treatment burden. Prompt and aggressive surgical intervention should be considered for postcataract fungal endophthalmitis.

The Variation of Electrical Pulse Duration Elicits Reliable Network-Mediated Responses of Retinal Ganglion Cells in Normal, Not in Degenerate Primate Retinas.

This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 µA and 500 to 4000 µs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm2 vs. 1.06 ± 0.09 mC/cm2, p < 0.05) at a 500 µs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm2, mouse; 1.04 ± 0.09 mC/cm2, and rat; 1.16 ± 0.16 mC/cm2, p < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics.

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans.

This study aimed to investigate the clinical characteristics of Korean patients with retinal dystrophy associated with pathogenic variants of cone rod homeobox-containing gene (CRX). We retrospectively enrolled Korean patients with CRX-associated retinal dystrophy (CRX-RD) who visited two tertiary referral hospitals. Pathogenic variants were identified using targeted panel sequencing or whole-exome sequencing. We analyzed clinical features and phenotypic spectra according to genotype. Eleven patients with CRX-RD were included in this study. Six patients with cone-rod dystrophy (CORD), two with macular dystrophy (MD), two with Leber congenital amaurosis (LCA), and one with retinitis pigmentosa (RP) were included. One patient (9.1%) had autosomal recessive inheritance, and the other ten patients (90.9%) had autosomal dominant inheritance. Six patients (54.5%) were male, and the mean age of symptom onset was 27.0 ± 17.9 years. At the first presentation, the mean age was 39.4 ± 20.6 years, and best-corrected visual acuity (BCVA) (logMAR) was 0.76 ± 0.90 in the better eye. Negative electroretinography (ERG) was observed in seven (63.6%) patients. Nine pathogenic variants were identified, including two novel variants, c.101-1G>A and c.898T>C:p.(*300Glnext*118). Taken together with the variants reported in prior studies, all variants within the homeodomain are missense variants, whereas most variants downstream of the homeodomain are truncating variants (88%). The clinical features of pathogenic variants within the homeodomain are either CORD or MD with bull's eye maculopathy, whereas variants downstream of the homeodomain cause more diverse phenotypes, with CORD and MD in 36%, LCA in 40%, and RP in 24%. This is the first case series in Korea to investigate the CRX-RD genotype-phenotype correlation. Pathogenic variants downstream of the homeodomain of the CRX gene are present as RP, LCA, and CORD, whereas pathogenic variants within the homeodomain are mainly present as CORD or MD with bull's eye maculopathy. This trend was similar to previous genotype-phenotype analyses of CRX-RD. Further molecular biologic research on this correlation is required.

Noncovalent antibody catenation on a target surface greatly increases the antigen-binding avidity.

Immunoglobulin G (IgG) antibodies are widely used for diagnosis and therapy. Given the unique dimeric structure of IgG, we hypothesized that, by genetically fusing a homodimeric protein (catenator) to the C-terminus of IgG, reversible catenation of antibody molecules could be induced on a surface where target antigen molecules are abundant, and that it could be an effective way to greatly enhance the antigen-binding avidity. A thermodynamic simulation showed that quite low homodimerization affinity of a catenator, e.g. dissociation constant of 100 µM, can enhance nanomolar antigen-binding avidity to a picomolar level, and that the fold enhancement sharply depends on the density of the antigen. In a proof-of-concept experiment where antigen molecules are immobilized on a biosensor tip, the C-terminal fusion of a pair of weakly homodimerizing proteins to three different antibodies enhanced the antigen-binding avidity by at least 110 or 304 folds from the intrinsic binding avidity. Compared with the mother antibody, Obinutuzumab(Y101L) which targets CD20, the same antibody with fused catenators exhibited significantly enhanced binding to SU-DHL5 cells. Together, the homodimerization-induced antibody catenation would be a new powerful approach to improve antibody applications, including the detection of scarce biomarkers and targeted anticancer therapies.

Cut-Off Value of Voluntary Peak Cough Flow in Patients with Parkinson's Disease and Its Association with Severe Dysphagia: A Retrospective Pilot Study.

Background and Objectives. Swallowing and coughing reflexes are both closely associated with airway protection. Peak cough flow (PCF) is associated with dysphagia in several neurogenic diseases. In this study, we aimed to analyze the relationship between PCF and aspiration in Parkinson's disease (PD) and determine the cut-off value of PCF. Materials and Methods. We retrospectively analyzed the records of patients with PD who underwent a videofluoroscopic swallowing study and checked for PCF. A total of 219 patients were divided into an aspiration group (n = 125) and a non-aspiration group (n = 94). Results. Significantly lower PCF values were observed in the aspiration group compared to the non-aspiration group (132.63 ± 83.62 vs. 181.38 ± 103.92 L/min, p < 0.001). Receiver operating characteristic curve analysis revealed that a PCF cut-off value of 153 L/min (area under the receiver operating characteristic curve, 0.648; sensitivity, 73.06%; specificity, 51.06%) was associated with aspiration in PD. Additionally, a univariate analysis showed that the male sex, lower body mass indexes, higher Hoehn and Yahr scales, and PCF values of ≤153 L/min indicated an increased risk of aspiration. Conclusions. Through a multivariate analysis, we demonstrated that a PCF value ≤153 L/min was associated with an increased risk of aspiration (odds ratio 3.648; 1.797-7.407), highlighting that a low PCF is a risk factor for aspiration in patients with PD.

New technology using crystalline lens autofluorescence for presbyopia and cataract grading.

PURPOSE: To investigate whether fundus autofluorescence (FAF) obtained using an ultra-wide field (UWF) fundus camera with an artificial opacity pattern can grade the degree of presbyopia and nuclear cataract. METHODS: Sixty eyes of 30 patients were enrolled in this prospective diagnostic study. The nuclear cataract (nuclear color/opalescence (NC/NO)) was graded according to the Lens Opacity Classification System III. The monocular near point of accommodation (NPA) was measured in eyes with NC3/NO3 or less. The mean gray value difference between the central 8 artificial opacity lesions and peripheral 8 artificial opacity lesions in the retinal AF was measured. The correlation between the mean gray value difference, NPA, and nuclear cataract grade was analyzed. RESULTS: The mean nuclear cataract grade of 60 eyes was 3.2 ± 1.6 and mean NPA of 37 eyes was 45.3 ± 16.1 cm. The mean gray value differences increased with increasing nuclear cataract grade (eyes with NC/NO grade 1, 53.3 ± 11.4; 2, 78.3 ± 13.6; 3, 95.2 ± 12.2; 4, 101.6 ± 11.9; 5, 109.0 ± 22.9; and 6, 121.1 ± 12.0; p < 0.001). The mean gray value difference was positively correlated with both the monocular NPA (R2 = 0.637; ß coefficient = 1.009; 95% CI, 0.748 to 1.271; p < 0.001) and nuclear cataract grade (R2 = 0.661; ß coefficient = 12.437; 95% CI, 10.097 to 14.778; p < 0.001). CONCLUSIONS: The FAF camera with an artificial opacity pattern attached can be used to effectively diagnose the degree of presbyopia and nuclear cataract.

Outer retinal degeneration in a non-human primate model using temporary intravitreal tamponade with N-methyl-N-nitrosourea in cynomolgus monkeys.

Objective:The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU).Approach:Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2-3 mg ml-1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed.Main results:Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved.Significance:Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.

An Outbreak of Fungal Endophthalmitis After Cataract Surgery in South Korea.

Importance: Fungal endophthalmitis caused by contaminated medical products is extremely rare; it follows an intractable clinical course with a poor visual prognosis. Objective: To report the epidemiologic and clinical features and treatment outcomes of a nationwide fungal endophthalmitis outbreak after cataract surgery as a result of contaminated viscoelastic agents in South Korea. Design, Setting, and Participants: This was a retrospective case series analysis of clinical data from multiple institutions in South Korea conducted from September 1, 2020, to October 31, 2021. Data were collected through nationwide surveys in May and October 2021 from the 100 members of the Korean Retinal Society. Patients were diagnosed with fungal endophthalmitis resulting from the use of the viscoelastic material sodium hyaluronate (Unial [Unimed Pharmaceutical Inc]). Data were analyzed from November 1, 2021, to May 30, 2022. Main Outcomes and Measures: The clinical features and causative species were identified, and treatment outcomes were analyzed for patients who underwent 6 months of follow-up. Results: The fungal endophthalmitis outbreak developed between September 1, 2020, and June 30, 2021, and peaked in November 2020. An official investigation by the Korea Disease Control and Prevention Agency confirmed contamination of viscoelastic material. All 281 eyes of 265 patients (mean [SD] age, 65.4 [10.8] years; 153 female individuals [57.7%]) were diagnosed with fungal endophthalmitis, based on clinical examinations and supportive culture results. The mean (SD) time period between cataract surgery and diagnosis was 24.7 (17.3) days. Patients exhibited characteristic clinical features of fungal endophthalmitis, including vitreous opacity (212 of 281 [75.4%]), infiltration into the intraocular lens (143 of 281 [50.9%]), and ciliary infiltration (55 of 281 [19.6%]). Cultures were performed in 260 eyes, and fungal presence was confirmed in 103 eyes (39.6%). Among them, Fusarium species were identified in 89 eyes (86.4%). Among the 228 eyes included in the treatment outcome analysis, the mean (SD) best-corrected visual acuity improved from 0.78 (0.74) logMAR (Snellen equivalent, 20/120 [7.3 lines]) to 0.36 (0.49) logMAR (Snellen equivalent, 20/45 [4.9 lines]) at 6 months. Furthermore, disease remission with no signs of fungal endophthalmitis (or cells in the anterior chamber milder than grade 1) was noted in 214 eyes (93.9%). Conclusions and Relevance: This was a retrospectively reviewed case series of a fungal endophthalmitis outbreak resulting from contaminated viscoelastic material. Findings of this case series study support the potential benefit of prompt, aggressive surgical intervention that may reduce treatment burden and improve prognosis of fungal endophthalmitis caused by contaminated medical products.

Predictive role of optical coherence tomography angiography for exudation recurrence in patients with type 1 neovascular age-related macular degeneration treated with pro-re-nata protocol.

OBJECTIVES: We sought to identify the consecutive changes and predictive features for exudation recurrence in macular neovascularization (MNV) using optical coherence tomography angiography (OCTA) in type 1 neovascular age-related macular degeneration (NVAMD). METHODS: A total of 291 OCTA images in consecutive visit of 45 patients newly diagnosed with type 1 NMV and treated with three loading intravitreal anti-vascular endothelial growth factor injections (IVIs) and a pro-re-nata (PRN) therapy regimen were analysed. Quantitative features of OCTA included the MNV area, MNV length, total number of endpoints (open-ended vessels) and junctions (internal branching) using AngioTool. Two subgroups were divided according to exudation recurrence time from the third IVI (group 1: ≤3 months vs. group 2: >3 months). RESULTS: The area, length, number of total junctions, and endpoints decreased during three loading IVIs and increased at exudation recurrence (all p < 0.05). In a subgroup analysis of consecutive OCTA images, the number of total endpoints increased at two months prior to exudate recurrence in group 2 (the late recurrence group, p = 0.020). A higher total number of endpoints of MNV at baseline were found to be related with group 1 (early recurrence, p = 0.020 and 0.012 in univariate and multivariate regression analyses). CONCLUSIONS: The MNV with higher open-ended vessels at the lesion periphery at baseline might be expected to show earlier recurrence of exudation after loading IVIs. By observing the number of open-ended vessels in consecutive OCTA images, exudation recurrence could be predicted.

Changes on optical coherence tomography angiography and fluorescein angiography in eyes with neovascular age-related macular degeneration.

AIM: To evaluate the changes on optical coherence tomography angiography (OCTA) and fluorescein angiography (FA) and their correlation in neovascular age-related macular degeneration (nAMD) before and after intravitreal aflibercept injections (IAIs). METHODS: In 43 treatment-naïve patients with nAMD, choroidal neovascularization (CNV) in OCTA were morphologically and quantitatively analyzed before and after IAIs to determine whether they are correlated with leakage on FA or not. By combining CNV in OCTA and leakage in FA, lesions were characterized as three types: L+C+ (with both CNV and leakage), L-C+ (with CNV but without leakage), or L+C- lesion (with leakage outside CNV). RESULTS: Before IAI, while 27 eyes had L+C+ lesion only, 16 eyes had both L+C+ and L-C+ lesions simultaneously. Tiny capillaries and anastomosis in CNV were more developed in L+C+ lesion, at 86.0% and 58.1%, respectively, relative to 9.3% and 9.3% in L-C+ lesions (P<0.001). After IAIs in 33 eyes, tiny capillaries and anastomosis were decreased in the lesions with cessation of leakage on FA (P<0.001 and P=0.001, respectively). In quantitative analysis, neovascularization length and numbers of junctions and endpoints were also significantly decreased. CONCLUSION: Leakage on FA is associated with CNV morphology in OCTA and remained so after IAIs. Therefore, by carefully assessing the morphological and quantitative changes of CNV in OCTA before and after treatment, activity of nAMD is expected even though CNV on OCTA is not completely matched with fluorescein leakage.

Structural changes in the retina after implantation of subretinal three-dimensional implants in mini pigs.

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-µm-high 3D electrodes on a 200-µm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-µm-thick sloped PDMS substrate without electrodes (group 2); and a 140-µm-thick sloped PDMS substrate with 20-µm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain-optical coherence tomography (SD-OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-µm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD-OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-µm-high electrodes showed better structural compatibility than the 75-µm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-µm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

CLINICAL IMPLICATION OF RETINAL NERVE FIBER LAYER SCHISIS AND MACULAR FLUORESCEIN LEAKAGE IN PRIMARY IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: We evaluated the relationship between macular fluorescein leakage and retinal nerve fiber layer (RNFL) schisis and investigated the visual prognostic values after pars plana vitrectomy (PPV) and idiopathic epiretinal membrane removal. METHODS: We analyzed the correlations between preoperative optical coherence tomography (OCT) parameters and macular leakage. The final best-corrected visual acuity and central macular thickness were compared according to the presence or absence of macular leakage and RNFL schisis. RESULTS: In 80 eyes with idiopathic epiretinal membrane treated with PPV and membrane peeling, preoperative macular leakage was associated with the presence of preoperative RNFL schisis and inner nuclear layer microcysts. Eyes with both macular leakage and RNFL schisis showed worse postoperative best-corrected visual acuity than those without both factors. CONCLUSION: In the presence of macular fluorescein leakage and RNFL schisis, postoperative best-corrected visual acuity is worse, and improvements in the central macular thickness are greater than those in the absence of both factors.

Vision-Threatening Ocular Adverse Events after Vaccination against Coronavirus Disease 2019.

A single-center retrospective observational case series was conducted. This case series enrolled patients who showed ophthalmic manifestations within one week after COVID-19 vaccination at Korea University Guro Hospital in Seoul, Korea, from May 2021 to January 2022. The medical records of patients who complained of ocular symptoms and showed ophthalmic adverse events within one week after COVID-19 vaccination were reviewed. Seventeen eyes from 16 patients with a mean age of 63.8 (range 33-83) years were included in the case series, and all symptoms developed within 1-7 days following inoculation. Retinal vein occlusion in nine eyes (52.9%), retinal artery occlusion in one eye (5.9%), newly developed anterior uveitis in one eye (5.9%), exacerbation of previously diagnosed panuveitis in two eyes (11.8%), and angle-closure attack with high intraocular pressure in four eyes (23.5%) were included. Twelve patients (75%) had been vaccinated with the AstraZeneca (AZD1222) and four (25%) with the Pfizer (BNT162b2) vaccines. Of these, 10 patients (62.5%) experienced ocular disease exacerbation after the first dose, 4 (25%) after the second dose, and 2 (12.5%) after the third dose (booster shot). Eleven patients (64.7%) underwent tests for hematological abnormalities, and three of them tested positive for anti-PF4 antibodies, but no abnormal findings were noted. A causal relationship between vaccination and the ocular manifestations could not be determined, which is a limitation of this study. However, clinicians should consider the effect of COVID-19 vaccination on ophthalmic disease. Further studies are required to elucidate the possible effects of COVID-19 vaccination on the eye.

Correlated Activity in the Degenerate Retina Inhibits Focal Response to Electrical Stimulation.

Retinal prostheses have shown some clinical success in patients with retinitis pigmentosa and age-related macular degeneration. However, even after the implantation of a retinal prosthesis, the patient's visual acuity is at best less than 20/420. Reduced visual acuity may be explained by a decrease in the signal-to-noise ratio due to the spontaneous hyperactivity of retinal ganglion cells (RGCs) found in degenerate retinas. Unfortunately, abnormal retinal rewiring, commonly observed in degenerate retinas, has rarely been considered for the development of retinal prostheses. The purpose of this study was to investigate the aberrant retinal network response to electrical stimulation in terms of the spatial distribution of the electrically evoked RGC population. An 8 × 8 multielectrode array was used to measure the spiking activity of the RGC population. RGC spikes were recorded in wild-type [C57BL/6J; P56 (postnatal day 56)], rd1 (P56), rd10 (P14 and P56) mice, and macaque [wild-type and drug-induced retinal degeneration (RD) model] retinas. First, we performed a spike correlation analysis between RGCs to determine RGC connectivity. No correlation was observed between RGCs in the control group, including wild-type mice, rd10 P14 mice, and wild-type macaque retinas. In contrast, for the RD group, including rd1, rd10 P56, and RD macaque retinas, RGCs, up to approximately 400-600 µm apart, were significantly correlated. Moreover, to investigate the RGC population response to electrical stimulation, the number of electrically evoked RGC spikes was measured as a function of the distance between the stimulation and recording electrodes. With an increase in the interelectrode distance, the number of electrically evoked RGC spikes decreased exponentially in the control group. In contrast, electrically evoked RGC spikes were observed throughout the retina in the RD group, regardless of the inter-electrode distance. Taken together, in the degenerate retina, a more strongly coupled retinal network resulted in the widespread distribution of electrically evoked RGC spikes. This finding could explain the low-resolution vision in prosthesis-implanted patients.

Pathogenic Risk Factors and Associated Outcomes in the Bullous Variant of Central Serous Chorioretinopathy.

PURPOSE: To compare the clinical features, treatments, and outcomes between bullous and chronic variants of central serous chorioretinopathy (CSC). DESIGN: Retrospective, observational case series. PARTICIPANTS: Sixty-two eyes of 44 patients with bullous-variant CSC (bvCSC) and 97 eyes of 85 patients with nonbullous CSC. METHODS: We conducted a national survey between September 1, 2020, and March 31, 2021, of members of the Korean Retina Society and obtained data of patients with bvCSC from 11 retinal centers. A comparator group comprised consecutive chronic CSC patients without bullous detachment. MAIN OUTCOME MEASURES: Baseline demographics and patient characteristics were compared between groups. Secondary outcomes included factors associated with visual prognosis within the bvCSC group. RESULTS: Compared with the nonbullous CSC group, the bvCSC group presented at a younger age (49 vs. 52 years; P = 0.047) and with more bilateral involvement (41% vs. 14%; P < 0.001). Systemic corticosteroid use was more prevalent in the bvCSC group, both in terms of any exposure (50% vs. 20%; P = 0.001) and long-term exposure (36% vs. 9%; P < 0.001). The bvCSC group had distinct imaging features (all P < 0.05): retinal folding (64% vs. 1%), subretinal fibrin (75% vs. 13%), multiple retinal pigment epithelium tears (24% vs. 2%), and multifocal fluorescein leakages with terminal telangiectasia (36% vs. 1%). Although bvCSC patients had worse vision at diagnosis (20/80 vs. 20/44; P = 0.003), treatment response was more robust (fluid resolution by final follow-up, 84% vs. 68%; P = 0.034) even with conservative management, resulting in similar final vision (20/52 vs. 20/45; P = 0.52). History of kidney-related (odds ratio [OR] 5.4; 95% confidence interval [CI] 1.3-18.5; P = 0.045) and autoimmune/rheumatoid diseases (OR 25.4, 95% CI 2.8-195.0; P = 0.004) showed associations with the bvCSC group. Apart from vision at diagnosis (OR 0.1, 95% CI 0.05-0.36; P < 0.001), a history of renal transplantation was most predictive of visual prognoses for bvCSC eyes (OR 0.2, 95% CI 0.04-0.75; P = 0.020). CONCLUSIONS: Bullous-variant CSC may be associated with pathogenic risk factors based on underlying medical conditions and systemic corticosteroid use. Poor vision at diagnosis and history of renal transplantation were associated with poor visual outcome.

Retinal Vessel Density in Age-Related Macular Degeneration Patients with Geographic Atrophy.

We compared the retinal vessel density and inner retinal thickness in patients who had one eye with geographic atrophy (GA) and a fellow eye with intermediate age-related macular degeneration (iAMD). The vessel density from the superficial vascular complex (SVC) and deep vascular complex (DVC) through optical coherence tomography angiography and the thickness of the nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer nuclear layer (ONL) on a structural optical coherence tomography thickness map were measured in 28 eyes of 14 GA patients with iAMD in the fellow eye. GA eyes had significantly lower vessel density in the SVC (26.2 ± 3.9% vs. 28.3 ± 4.4%; p = 0.015) and DVC (24.2 ± 2.6% vs. 26.8 ± 1.9%; p = 0.003) than fellow eyes (iAMD). GCIPL and ONL were significantly thinner in GA eyes than in the fellow eyes (p = 0.032 and 0.024 in the foveal areas, p = 0.029 and 0.065 in the parafovea areas, respectively). Twenty-four eyes of 12 patients were followed up for 2 years and seven of the fellow eyes (58.3%) developed GA during the follow-up period and showed reduced vessel density in the SVC (26.4 ± 3.0% vs. 23.8 ± 2.9%; p = 0.087) and DVC (25.8 ± 2.2% vs. 22.4 ± 4.4%; p = 0.047) compared to baseline. Vessel density and GCIPL thickness map measurements are potential GA markers in non-neovascular AMD.