Quantitative evaluation of choroidal and retinal microvasculature post-alcohol consumption: A pilot study.

PURPOSE: The aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking. METHODS: Healthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption. RESULTS: A total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05). CONCLUSIONS: Excessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration.

PURPOSE: To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm3) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm2) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL). RESULTS: Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (ß = 0.377, P < 0.001), avascular SHRM (ß = 0.306, P = 0.032), and ELM impairment area (ß = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (ß = 0.374, p = 0.003; ß = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (ß = 0.475, P < 0.001). CONCLUSION: The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

EPIRETINAL MACROPHAGE-LIKE CELLS ON OPTICAL COHERENCE TOMOGRAPHY: Potential Inflammatory Imaging Biomarker of Severity in Diabetic Retinopathy.

PURPOSE: To investigate the clinical value of epiretinal macrophage-like cells (eMLCs) in different stages of diabetic retinopathy (DR), including diabetic macular edema (DME). METHODS: One hundred and seventy-six eyes of 176 patients, including 31 diabetes eyes without retinopathy, 24 with mild nonproliferative DR (NPDR), 37 with moderate NPDR, 32 with severe NPDR, and 52 with proliferative DR, were compared with 30 healthy controls. The optic nerve head and macular region were examined using en face optical coherence tomography and optical coherence tomography angiography. A previously described technique was employed to measure the eMLCs on the inner limiting membrane. RESULTS: The optic nerve head and macular eMLC densities increased with worsening DR stage and were higher in moderate, severe NPDR, and proliferative DR, especially in eyes with DME (all adjusted P < 0.01). The optic nerve head and macular eMLC densities in the DME groups were higher than those in their corresponding non-DME groups at the same DR stage (all P < 0.05). The average macular thickness was correlated with macular eMLC density (standardized ß = 0.661, P < 0.001) in patients with diabetes. The proportion of eyes with larger and plumper eMLCs increased with worsening DR and was higher in moderate, severe NPDR, proliferative DR, and eyes with DME ( P = 0.018, P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSION: Increased density along with morphological changes of eMLCs is observed beginning with moderate NPDR and correlates with the progression of DR, including DME.

Natural course of age-related retentional avascular pigment epithelial detachment: Support for the lipid barrier hypothesis.

PURPOSE: Retentional pigment epithelial detachment (PED) associated with age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) is hypothesized to be caused by Bruch's membrane's lipid barrier. This study aimed to report the natural course of retentional PED and evaluate the relationship between retentional PED evolution and ASHS-LIA. METHODS: Patients with treatment-naïve retentional PED were enrolled and observed every 3 months for at least 12 months. Treatment was not performed except for secondary macular neovascularization. RESULTS: In 55 studied eyes with a median follow-up of 18.0 (range: 12-36) months, 87.3% (48/55) of the retentional PEDs persisted, 7.3% (4/55) resolved, and 5.5% (3/55) progressed to polypoidal choroidal vasculopathy. The mean PED area significantly increased during the follow-up (P <0.001) and with the ASHS-LIA grade at each follow-up point (all P <0.05), especially during the first 6 months before approaching the edge of confluent ASHS-LIA. Persistent PEDs were mostly stable (52.1%) or enlarged (45.8%) but reduced in only 1 case (2.1%) due to RPE microrip at the edge of PED. The persistent PEDs were all within the ASHS-LIA region, especially the macular confluence region. The resolved PEDs all had grade 1 ASHS-LIA and resolved after gradual expansion of PED beyond the confluent ASHS-LIA region. PEDs that progressed to MNV all had confluent grade 2 or 3 ASHS-LIA. RPE breaks or apertures within PED did not affect the progression of the PED. CONCLUSION: The natural course of retentional PED is closely related to the features of ASHS-LIA and supports its lipid-barrier hypothesis.

SOLITARY PUNCTATE CHORIORETINITIS: A Unique Subtype of Punctate Inner Choroidopathy.

PURPOSE: To describe a case series of a special subtype of punctate inner choroidopathy with solitary lesions in the macular area and named solitary punctate chorioretinitis. METHODS: This retrospective observational study clinically evaluated 12 eyes from 12 patients diagnosed as punctate inner choroidopathy with solitary lesions. Demographic data and multimodal imaging features were analyzed for the included patients. RESULTS: All the included patients were Chinese and of Han ethnicity. The median age of the included patients was 29.5 years (range: 25-40 years). Most patients (11/12, 91.67%) were myopic, with median refraction errors of -4.4 diopters (D) (range: -8.5 to 0 D). Solitary chorioretinitis lesions were yellow‒white and appeared hyperfluorescent during the entire phase of fundus fluorescein angiography without leakage (9/12, 75%) and hypofluorescent on indocyanine green angiography (11/11, 100%). On spectral domain optical coherence tomography, active inflammatory lesions appeared as isolated, heterogeneous, moderately reflective material at the outer retina (10/12, 83.33%) in the fovea or parafoveal region with disruption of the outer retinal layers. When the inflammatory lesions regressed, the moderately reflective materials in the outer retina were absorbed or regressed with outer retinal tissue loss. Additional sequelae of lesion regression included focal choroidal excavation and intraretinal cystoid space. Secondary choroidal neovascularization was noticed in 2 eyes (2/12, 16.67%). CONCLUSION: Solitary punctate chorioretinitis is a rare and unique subtype of punctate inner choroidopathy. Solitary punctate chorioretinitis may also be an unrecognized etiology of some forms of focal choroidal excavation and idiopathic choroidal neovascularization.

CORRELATION BETWEEN FOCAL CHOROIDAL EXCAVATION AND UNDERLYING RETINOCHOROIDAL DISEASE: A Pathological Hypothesis From Clinical Observation.

PURPOSE: To evaluate focal choroidal excavation (FCE) in eyes with various diseases using multimodal imaging modalities and to investigate the correlation of FCE and underlying chorioretinal diseases. METHODS: This retrospective observational study included 62 eyes from 56 patients who were identified by optical coherence tomography as having FCE. All included patients underwent comprehensive clinical examinations and multimodal imaging to identify and detect the characteristics of FCE and its correlation with underlying chorioretinal diseases. RESULTS: All included patients were of Chinese descent, and the median age at diagnosis was 43 years (range: 15-66). Seventy-three FCEs appeared in these included eyes. Most FCEs were formed at sites with anatomical changes caused by various chorioretinal diseases. Choroidal osteoma, punctate inner choroidopathy, and central serous chorioretinopathy were the most common etiologies of FCE. During follow-up, 14 eyes (22.58%) exhibited a pattern change and three eyes (4.84%) developed new-onset choroid neovascularization. CONCLUSION: Focal choroidal excavation is a common sign found in a variety of chorioretinal diseases. Processes that involve impairment or tissue loss of the outer retina and inner choroid and disrupt the balance of intraocular pressure and choroidal pressure because of mechanical disturbance may play a role in FCE formation.

Screening for diabetic retinopathy in diabetic patients with a mydriasis-free, full-field flicker electroretinogram recording device.

PURPOSE: To investigate the accuracy of the RETeval full-field flicker ERG in the screening of diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) and to determine a suitable range of DR diagnostic reference for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 172 subjects with T2DM, including 71 subjects without clinically detectable DR (NDR), 25 subjects with mild non-proliferative diabetic retinopathy (NPDR), 24 subjects with moderate NPDR, 27 subjects with severe NPDR and 25 subjects with proliferative diabetic retinopathy (PDR). All the subjects underwent a full-field flicker ERG using the RETeval device (DR assessment protocol), which is a mydriasis-free, full-field electroretinogram (ERG) recording system. The performance of the DR assessment protocol in detecting the DR (including mild NPDR, moderate NPDR, severe NPDR and PDR) and VTDR was analyzed with the receiver operating characteristic (ROC) curve. RESULTS: For the detection of DR (mild NPDR, moderate NPDR, severe NPDR, PDR), the area under the ROC curve was 0.867 (p < 0.001, 95% CI 0.814-0.920), and the best cutoff value for DR was determined to be 20.75, with a sensitivity of 80.2% and specificity of 81.7%. Meanwhile, for the detection of VTDR, the area under the ROC curve was 0.965 (p < 0.001, 95% CI 0.941-0.989), and the best cutoff value was set to 23.05, with a sensitivity of 94.6% and a specificity of 88.8%. CONCLUSION: The DR assessment protocol in RETeval device was effective in screening for DR (mild NPDR, moderate NPDR, severe NPDR, PDR) and VTDR in patients with diabetes. It could be helpful in referring and managing patients with T2DM in primary healthcare setting. However, caution should be taken that optimal cutoff value of DR assessment protocol may vary in different ethnic populations.

Retinal vasculature-function correlation in non-proliferative diabetic retinopathy.

PURPOSE: To compare and correlate retinal microcirculation and function in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: Thirty-three healthy controls (33 eyes), 36 diabetic patients with no clinically detectable retinopathy (NDR, 36 eyes) and 101 patients (101 eyes) with NPDR (35 mild NPDR, 34 moderate NPDR, 32 severe NPDR) were involved in the study. We used optical coherence tomography angiography (OCTA) to quantify the macular vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP) and foveal density in a 300 µm region around foveal avascular zone. Retinal function was assessed by a mydriasis-free, full-field flicker electroretinogram (FERG) recording device, and the amplitudes and implicit time were recorded. The association between microvascular parameters and FERG results was analyzed with stepwise multiple linear regression model. RESULTS: Decreased amplitudes and delayed implicit time, as well as lower parafoveal/perifoveal VD in both SCP and DCP, were found in NDR group and NPDR groups compared with the control group (all p < 0.05). Specifically, the FERG parameters and microvascular indices were comparable between NDR group and mild NPDR group (all p > 0.05). However, compared to mild NPDR, the reduction in FERG amplitude was more pronounced than the reduction in parafoveal VD (both SCP and DCP) in severe NPDR. Stepwise multiple linear regression analyses showed that delayed implicit time was significantly correlated with increased age and decreased VD of parafoveal region in both SCP and DCP in patients with NPDR. Meanwhile, decreased amplitude was significantly associated with decreased VD of parafoveal region in both SCP and DCP in patients with NPDR. CONCLUSION: Macular VD in both superficial and deep capillary plexus correlated with ERG implicit time and amplitude in mild-to-severe NPDR. OCTA and FERG may both be useful in detection of preclinical DR and early DR, but once the disease deteriorates, FERG may be more sensitive to discern progression of DR.

Comprehensive analysis of vitreous chemokines involved in ischemic retinal vein occlusion.

Purpose: To investigate vitreous levels of chemokines in eyes with ischemic retinal vein occlusion (RVO). Methods: The vitreous humor was collected at the start of 23-gauge pars plana vitrectomy from patients with ischemic RVO and patients with idiopathic preretinal membranes (PRMs) and idiopathic macular holes (IMHs). The levels of 40 different chemokines were measured using magnetic color-bead-based multiplex assay. The chi-square test was performed for clinical variables such as sex, and the Mann-Whitney U test was performed to evaluate the differences in the chemokine levels between the RVO group and the control group. Results: Vitreous humor was collected from 20 controls and 25 subjects with ischemic RVO. C-C motif ligand 17 (CCL17) was unmeasurable in more than 70% of the samples. The levels of 29 of 39 chemokines were statistically significantly elevated in the RVO group compared with the control group, including CCL21, C-X-C motif ligand (CXCL) 13, CCL27, CCL24, CX3CL1, CXCL6, interferon-gamma (IFN-γ), interleukin (IL) 1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-16, CXCL10, CXCL11, CCL8, CCL7, CCL13, CCL22, macrophage migration inhibitory factor (MIF), CXCL9, CCL3, CCL15, CCL20, CCL19, CCL23, CCL25, and tumor necrosis factor-alpha (TNF-α). Among the 29 elevated chemokines, we found that the levels of three chemokines (IL-8, CXCL9, and TNF-α) showed a more than six-fold increase in the RVO eyes versus controls, and CXCL9 expression showed the greatest change of all tested chemokines. Conclusions: Dozens of chemokines were found to be elevated in the vitreous of RVO eyes complicated with vitreous hemorrhage, suggesting that inflammation is severe in the ischemic retina. The knowledge of specific upregulation of chemokines in ischemic RVO could allow more targeted future therapies.

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy.

IMPORTANCE: Whether neural or vascular defects occur first in the early onset of diabetic retinopathy (DR) is undetermined. BACKGROUND: To investigate microcirculation and microstructure differences of optic nerve head (ONH) between diabetic eyes without clinically evident retinopathy and healthy controls using optical coherence tomography angiography (OCTA). DESIGN: Cross-sectional observational study. PARTICIPANTS: Sixty eyes of 60 patients with type 2 diabetes and without clinically evident retinopathy and 60 eyes of 60 age-matched healthy controls were included in this study. METHODS: All participants underwent 4.5 × 4.5-mm rectangle scans centred on the ONH using OCTA (RTVue-XR Avanti; Optovue, Fremont, CA). MAIN OUTCOME MEASURES: Peripapillary retinal nerve fibre layer (RNFL) thickness and capillary perfusion density inside the ONH and in the peripapillary region were compared between the two groups. RESULTS: Vessel density values in both peripapillary and inside the disc were significantly lower in diabetic patients without DR compared to normal controls. The reduction of vessel density was prominent in all eight peripapillary sectors in diabetic eyes (all P < 0.05). Thinning of RNFL thickness was significant in the nasal superior (P < 0.001), inferior nasal (P = 0.023) and superior nasal quadrant (P < 0.001) in diabetic eyes in comparison to normal controls. CONCLUSIONS AND RELEVANCE: ONH perfusion and peripapillary RNFL thickness were significantly decreased in preclinical DR patients compared to normal controls. Microvascular alterations in ONH may occur earlier than peripapillary RNFL defect in the course of DR.

Multimodal Imaging in Diagnosing Multiple Evanescent White Dot Syndrome following Human Papillomavirus Vaccine Immunization.

Purpose. This study presents a case of multiple evanescent white dot syndrome (MEWDS) following the administration of the second dose of a human papillomavirus vaccine (HPV). We conducted a review of the literature on vaccine-associated MEWDS. Observations. A 23-year-old Chinese female reported central scotomata in the left eye persisting for 3 weeks. Upon further inquiry, she had received the second dose of the human papillomavirus vaccine (Gardasil-9) three days before the onset of symptoms. A diagnosis of MEWDS was established based on clinical and multimodal imaging (MMI) data. Symptoms resolved after twelve weeks of oral prednisone treatment. Conclusion and Importance. This case highlights a typical case of MEWDS closely associated with HPV vaccination, demonstrating a favorable prognosis with MMI. Given the self-limiting nature of MEWDS, there is a risk of clinical misdiagnosis or oversight. While further studies are warranted to establish a definitive link between the HPV vaccine and MEWDS, this case suggests a potential connection. Healthcare practitioners should remain vigilant regarding possible ocular side effects associated with immunizations.

Incidence and multimodal imaging characteristics of macular neovascularisation subtypes in Chinese neovascular age-related macular degeneration patients.

AIMS: To investigate the incidence of macular neovascularisation (MNV) subtypes of neovascular age-related macular degeneration (nAMD) and summarise these subtypes' clinical features in the Chinese population using multimodal imaging. METHODS: We retrospectively analysed 506 consecutive treatment-naïve nAMD patients (582 eyes). Incidence of MNV subtypes and clinical features were recorded based on their multimodal images. The classification of MNV subtypes in nAMD patients were referred to Consensus on Neovascular Age-related Macular Degeneration Nonmenclature (CONAN) study group classifications. RESULTS: 460 eyes of 389 nAMD patients were included in our study. 68.5% (315/460) of nAMD eyes were from male. According to CONAN, we identified type 1 macular neovascularisation (MNV) in 61.1% of eyes (281/460), type 2 MNV in 16.3% of eyes (75/460), type 3 MNV in 2.0% of eyes (9/460), mixed type 1 and type 2 MNV in 20.6% of eyes (95/460). 58% of eyes (267/460) were diagnosed as polypoidal choroidal vasculopathy lesions (PCV). 45.2% of eyes (208/460) with PCV lesions were type 1 MNV and 12.8% of eyes (59/460) with PCV lesions were co-occurred with type 2 MNV. CONCLUSION: Based on the consensus anatomical classification system developed by the CONAN Study Group, we updated the incidence of MNV subtypes and found that PCV was the most common subtype and type 3 MNV was the least common subtype among Chinese nAMD patients. In addition, the co-occurrence of PCV and type 2 MNV was typically observed, and its frequency was reported in our study.

A Novel Exploration of the Choroidal Vortex Vein System: Incidence and Characteristics of Posterior Vortex Veins in Healthy Eyes.

Purpose: The purpose of this study was to investigate the incidence and characteristics of posterior vortex veins (PVVs) in healthy eyes and explore their relationship with age and refractive status. Methods: This retrospective cross-sectional analysis encompassed 510 eyes from 255 consecutive healthy participants. Wide-field optical coherence tomography angiography (WF-OCTA) imaging was used to assess the presence of PVVs. Eyes were classified according to refractive status (emmetropia, low and moderate myopia, and high myopia) and age (minors and adults). The incidence and characteristics of eyes with PVVs were analyzed. Results: Participants (mean age = 30.60 ± 21.12 years, 47.4% men) showed a mean refractive error of -2.83 ± 3.10 diopters (D; range = -12.00 to +0.75). PVVs were observed in 16.1% (82/510) of eyes. Of these, 39% (32/82) had PVVs in one eye and 61% (50/82) in both eyes. The mean number of PVVs per eye was 1.65 ± 1.05 (range = 1-6). PVVs are mainly around the optic disc (78%, 64/82) of eyes with PVVs and less in the macular area (6.1%, 5/82) or elsewhere (15.9%, 13/82). PVV incidence correlated with refractive status: 10.3% (22/213) in emmetropia, 16.6% (31/187) in low and moderate myopia, and 26.4% (29/110) in high myopia (P = 0.001), but not with age. Refractive status was the key predictor of PVV occurrence (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.02-2.06, P = 0.038). Conclusions: This study confirms PVVs' presence in healthy eyes, highlighting their inherent existence and susceptibility to alterations due to refractive conditions. These findings enhance our understanding of the vortex vein system and its distribution within the eyes.

Diurnal Variation in Choroidal Parameters Among Healthy Subjects Using Wide-Field Swept-Source Optical Coherence Tomography Angiography.

Purpose: The purpose of this study was to evaluate the diurnal variation in choroidal parameters in a wide field area among healthy subjects and to identify correlations between choroidal luminal area and stromal area and various systemic factors. Methods: In this cross-sectional study, 42 eyes from 21 healthy participants (mean age = 32.4 ± 8.8 years) were examined using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA, 24 mm × 20 mm). Measurements of choroidal parameters, including choroidal volume (CV), choroidal thickness (CT), choroidal vessel volume (CVV), and choroidal stromal volume (CSV), were taken at 8:00, 12:00, 18:00, and 22:00. Systemic factors, such as blood pressure and heart rate, were concurrently monitored. Results: Our study observed significant diurnal variations in the mean total CV, CT, CVV, and CSV, with minimum measurements around 12:00 (P < 0.001) and peak values at 22:00 (P < 0.001). Furthermore, changes in CV in specific regions were more closely associated with fluctuations in CVV than CSV in the same regions. No significant diurnal variations were found in systolic (P = 0.137) or diastolic blood pressure (P = 0.236), whereas significant variations were observed in the heart rate (P = 0.001). Conclusions: Our study reveals diurnal variations in choroidal parameters and their associations, emphasizing that changes in choroidal volume relate more to the luminal than the stromal area in vessel-rich regions. This enhances our understanding of choroidal-related ocular diseases. Translational Relevance: Regions with higher choroidal vasculature observed greater choroidal volume changes.

A prospective observation of influence of anti-VEGF on optic disc vasculature in nAMD patients.

BACKGROUND: This study aims to investigate the short-term changes in relatively normal retinal vessels following anti-vascular endothelial growth factor (anti-VEGF) therapy in nAMD patients, an area that currently represents a research gap. METHODS: In this prospective study, we enrolled patients newly diagnosed with neovascular age-related macular degeneration (nAMD) and received standardized monthly anti-VEGF therapy for three months. Follow-ups were conducted at baseline and 1-week, 1-month, 2-months and 3-months post first injection. Assessment indicators included radial peripapillary capillary vascular density (RPC-VD) and retinal nerve fiber layer (RNFL) thickness in different optic disk regions using optical coherence tomography angiography, as well as intraocular pressure (IOP). RESULTS: 68 nAMD patients (68 eyes) were included in this study. Significant reductions of RPC-VD and increases of RNFL thickness primarily in the nasal regions were observed 1-week post anti-VEGF (adjusted P < 0.05). Significant negative correlations were found between 1-week changes in RPC-VD and RNFL thickness in the nasal sectors (P < 0.05). From 1 to 3 months post-injection, RPC-VD and RNFL thickness essentially returned to baseline levels. Throughout the follow-up periods, IOP remained stable (P > 0.05). CONCLUSION: Anti-VEGF treatments transiently influence the relatively normal retinal vessels, which might lead to nerve fiber edema, predominantly on the nasal side of the optic disk.

Macrophage-like Cells Characterized by En Face Optical Coherence Tomography was Associated with Fluorescein Vascular Leakage in Behçet's Uveitis.

PURPOSE: To investigate the features of macrophage-like cell (MLC) characterized by en face optical coherence tomography (OCT) in Behçet's uveitis (BU). METHODS: The extent of fluorescein vascular leakage (FVL) was graded on a scale of 0-3 (0=none, 1=mild, 2=moderate, 3=severe) for the optic nerve head (ONH), macula and peripheral retina. The 3µm en face OCT slabs on inner limiting membrane of ONH or macular region was used to visualize the MLCs. RESULTS: The MLC densities of BU group in ONH and macular region were significantly higher than the control group (both p<0.001). The ONH and macular MLC density were significantly higher in eyes with higher FVL grade and they were positively correlated with FVL score (all p<0.001). CONCLUSION: MLC density was elevated in Behçet's uveitis and it may serve as a noninvasive indicator for the severity of fluorescein leakage and retinal inflammation in Behcet's uveitis.

Choroidal Vein Alterations in Pachychoroid Disease With Choroidal Vascular Hyperpermeability: Evaluated by Wide-Field Indocyanine Green Angiography.

Purpose: The purpose of this study was to investigate choroidal vein (ChV) morphological features in pachychoroid disease (PCD) with choroidal vascular hyperpermeability (CVH). Methods: This retrospective study assessed subfoveal choroidal thickness (SFCT) and CVH area numbers and locations of recruited patients with PCD using multimodal images. ChV alteration patterns, including fusiform, bulbosity, sausaging, confluence, and anastomoses, as well as asymmetric ChVs, dominant ChVs, and non-dominant ChVs, were evaluated using wide-field indocyanine green angiograms. Results: Of 68 PCD eyes from 35 patients (mean age: 46.16 ± 6.28 years, 71.4% men), 2.9% had uncomplicated pachychoroid, 32.4% had pachychoroid pigment epitheliopathy (PPE), 55.9% central serous chorioretinopathy (CSC), and 8.8% pachychoroid neovasculopathy (PNV). Mean SFCT was 468.65 ± 131.40 µm. Among 419 CVH areas, ChV fusiform, ChV bulbosity, and ChV sausaging accounted for 35.8%, 35.1%, and 29.1%, respectively; 21.2% had ChV confluence and 11.9% had ChV anastomoses. At CVH areas, 13.1% had retinal pigment epithelium (RPE) leakage. ChV fusiform is steadily declining (37.4%, 36.8%, and 22.9%, respectively), and ChV sausaging, ChV anastomoses, and ChV confluence are increased gradually in the PPE, CSC, and PNV groups (21.4%, 30.0%, and 37.1%; 11.4%, 11.1%, and 20.0%; and 19.8%, 20.9%, and 28.6%, respectively). Dominant ChVs had higher CVH area numbers than non-dominant ChVs in the PPE and CSC groups (P = 0.010, P = 0.001). Conclusions: Different patterns of ChV alterations, including the newly identified ChV confluence, are commonly present at CVH areas in PCD. The CVH areas in PCD eyes are primarily located within the dominant ChVs. These findings provide crucial evidence for advancing our understanding of the underlying mechanisms of PCD pathogenesis.

Changes in macrophage-like cells characterized by en face optical coherence tomography after retinal stroke.

Purpose: The retina could serve as a window of neuroinflammation, but the in vivo changes in macrophage-like cell (MLC), such as microglia, in acute ischemic retinal stroke remain unclear. Thus, the current study aimed to investigate the in vivo changes in MLC characterized by en face optical coherence tomography (OCT) after acute ischemic retinal stroke. Methods: Twenty patients with unilateral acute nonarteritic reperfused central retinal artery occlusion (CRAO) were participated in this study, and their contralateral eyes served as control group. A 3 µm en face OCT slab on the inner limiting membrane of the optic nerve head (ONH) region or macular region was used to visualize and binarize the MLCs. The MLCs were binarized and quantified using a semiautomated method. OCT angiography was used to evaluate the reperfusion status and obtain the structural data of the inner retina in the ONH and macula. The thickness of the ganglion cell complex in the macular region was measured. The optical intensity and optical intensity ratio of the inner retina were calculated to evaluate the ischemia severity. Results: In the ONH region, decreased vessel densities of radial peripapillary capillaries accompanied by increased thickness of the retinal nerve fiber layer were found in the CRAO eyes in comparison to the unaffected eyes (p=0.001, p=0.009, respectively). In the macular region, significantly lower vessel densities in both the superficial and deep capillary plexus and increased thickness of the ganglion cell complex were also found in the CRAO eyes (all p ≤ 0.001). The ONH and macular MLC quantities and densities in CRAO eyes were significantly higher than those in the unaffected eyes (both p<0.001). Larger and plumper MLCs were observed in the CRAO eyes compared with their unaffected eyes. ONH and macular MLC densities were positively associated with the disease duration in the acute phase and the optical intensity ratio of inner retina. Conclusions: The increased density and morphological changes of MLCs may indicate the aggregation and activation of MLCs following acute reperfused CRAO. The aggregation of MLCs may be more pronounced in CRAO eyes with longer disease duration and more severe ischemia. MLCs characterized by en face OCT may serve as an in vivo visual tool to investigate neuroinflammation in the ischemic-reperfusion process of stroke.

Detection of pachychoroid neovasculopathy with optical coherence tomography angiography versus dye angiography imaging.

BACKGROUND: To investigate the sensitivity and specificity of optical coherence tomography angiography (OCTA) versus dye angiography for detecting pachychoroid neovasculopathy (PNV) and to determine the morphological factors that affect PNV detection. METHODS: Patients with pachychoroid phenotype were prospectively enrolled and underwent multimodal imaging examinations during the same visit. The diagnostic accuracy of fundus fluorescein angiography (FFA), FFA combined with indocyanine green angiography (ICGA) and OCTA for PNV was evaluated using multimodal imaging as the reference. Multimodal parameters of PNV were qualitatively and quantitatively assessed. RESULTS: PNV was detected in 58 eyes (46 patients) out of 340 pachychoroid eyes (201 patients) according to reference standard. Patients with PNV eyes were significantly older (54.6±7.56 vs. 48.2±9.1 years), were more likely to have a chronic central serous chorioretinopathy history (CSC) (93.1% vs. 12.4%) and had a worse visual acuity (0.30±0.22 vs. 0.58±0.30) than those without PNV eyes (all P<0.001). The sensitivity of FFA, FFA combined with ICGA, and OCTA in detecting PNV in patients with the pachychoroid phenotype was 67.2%, 63.8% and 98.3%, respectively, and the specificity was 87.2%, 96.8% and 100.0%, respectively. PNV not identified by dye angiography was more manifested as the absence of late plaque hypercyanescence on ICGA (P<0.001) and overall smaller capillaries without a distinct pattern (P=0.001), fewer core vessels (P=0.002) and smaller area (P=0.044). CONCLUSIONS: OCTA showed superior detection rate and accuracy for identifying PNV over dye angiography. In case multimodal imaging is unavailable, OCTA can be an effective and noninvasive method for monitoring PNV and guiding treatment decisions.

Evaluation of short-term intraocular pressure changes after intravitreal injection of Conbercept in patients with diabetic macular edema.

Background: The study concerning the influence of Conbercept, which is an anti-Vascular endothelial growth factor (VEGF) agent, in intraocular pressure (IOP) spike is limited and warrants further investigation. The current study aimed to investigate the changes of intraocular pressure after intravitreal injection (IVI) of Conbercept and evaluate the risk factors associated with intraocular pressure spikes. Methods: Patients with diabetic macular edema receiving intravitreal injection of 0.05 ml (0.5 mg) Conbercept were involved in the study. All patients underwent slit lamp examination to determine the status of phakia/pseudophakia. The axial length was measured using IOL Master 500 before intravitreal injection. Patients underwent a Conbercept intravitreal injection with a 30-gauge needle in a standard fashion. The intraocular pressure was measured 2 min before injection, and 2, 10, 30 min, 1, 2, 5, 24 h after injection using a rebound tonometer. The changes of intraocular pressure and the relevant risk factors were evaluated. Patients were subdivided into phakic group and pseudophakic group to analyze the effect of lens status on intraocular pressure changes. Results: Forty patients with a mean age of 62.48 ± 12.22 years were included in the study. The mean intraocular pressure values at baseline and 2, 10, 30 min, 1, 2, 5, 24 h after injection were 14.81 ± 3.13 mmHg, 26.80 ± 9.43 mmHg, 18.76 ± 6.16 mmHg, 16.54 ± 5.94 mmHg, 15.64 ± 3.75 mmHg, 14.46 ± 3.03 mmHg, 14.10 ± 1.88 mmHg, 14.23 ± 2.71 mmHg respectively. The intraocular pressure after injection for 2, 10 min was significantly higher than baseline (p < 0.001, p = 0.001, respectively). The intraocular pressure between baseline and post-injection for 30 min or beyond were comparable (all p > 0.05). No significant difference was found between the phakic group and pseudophakic group (p = 0.422). The changes of intraocular pressure were positively correlated with age (r = 0.329, p = 0.038), but negatively with axial length (r = -0.472, p = 0.002). Conclusion: intravitreal injection of Conbercept may cause rapid spike of intraocular pressure, but is safe with respect to short-term changes. The intraocular pressure in patients with older age and shorter axial length is more likely to be higher after intravitreal injection.