PURPOSE:To characterize persistent diffuse photoreceptor disorganization, a newly recognized retinal disorder, and establish diagnostic criteria differentiating it from similar outer retinopathies. METHODS:This retrospective observational case series included 14 patients (21 eyes) with subacute vision loss, unremarkable fundus, and persistent diffuse photoreceptor disorganization on optical coherence tomography, from 2020 to 2025. Medical records, multimodal imaging (optical coherence tomography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography), and visual function (electroretinography, visual field) findings were analyzed. RESULTS:Patients (mean age 30.7 years) presented with subacute vision loss [mean best-corrected visual acuity 0.9 LogMAR (20/160), range, 2.0-0.2 (FC-20/32)]. Seven patients (50%) had bilateral involvement. Infectious uveitis and known retinal dystrophy mutations (via whole-exome sequencing) were excluded. Fundus, fundus autofluorescence, and indocyanine green angiography were largely unremarkable. Optical coherence tomography revealed blurred/rough ellipsoid zone and absent interdigitation zone in the posterior pole of all eyes (including fovea in 100% of eyes, periphery in 95.2%). The retinal pigment epithelium layer was preserved. Outer retina thickness was significantly thinner in involved eyes compared with fellow eyes (118.3 vs. 147.6 µ m, P = 0.031). Fundus angiography showed peripheral venous leakage in 75% of eyes. Full-field electroretinography indicated reduced amplitudes (normal latency, scotopic/photopic), and visual fields showed significant defects. Eleven patients received immunosuppressive therapies. Over 17 months, optical coherence tomography abnormalities persisted, outer retina thickness slowly decreased, and visual acuity remained stable with gradual deteriorations in some patients. CONCLUSION:Persistent diffuse photoreceptor disorganization is characterized by subacute, diffuse, and persistent photoreceptor disorganization with largely unremarkable fundus, distinct from other outer retinopathies. Visual prognosis is generally poor, necessitating further research into pathogenesis and treatment.

BACKGROUND:Hard drusen appear as hyperfluorescent dots on indocyanine green angiography (ICGA) due to their high phospholipid content. This study aims to explore the distribution of peripheral hard drusen across age groups and retinal regions, and their correlation with macular pathology including hard drusen, soft drusen, and progression to neovascular age-related macular degeneration (nAMD). METHODS:A hospital-based retrospective study was conducted at Zhongshan Ophthalmic Center. Patients who underwent ICGA over a five-year period were included and categorised into seven age groups. Hard drusen were quantified across nine retinal quadrants using the Trainable Weka Segmentation machine learning plugin. A subgroup of patients underwent imaging follow-up to assess progression to nAMD. RESULTS:Here we show, across 1562 normal eyes (14,058 ICGA images) quantified using a validated machine learning model (Dice coefficient: 0.697; sensitivity: 82.93%; ICC: 0.944), that age 50 represents a critical threshold for drusen accumulation, with significant increases observed across all nine quadrants. The nasal quadrants demonstrate earlier and more prominent drusen accumulation compared to the temporal quadrants (P < 0.001 across ages 20-69 years). Notably, the central superior quadrant shows consistent associations with macular hard drusen counts (Stdβ = 0.104, P = 0.010), soft drusen volume (ρ = 0.657, P = 0.020), and progression to nAMD (OR = 1.324, P = 0.040). CONCLUSIONS:Peripheral hard drusen accumulate preferentially in the nasal quadrants and increase markedly after age 50. Comprehensive peripheral retinal evaluation during ICGA examination may hold potential clinical value for AMD monitoring, pending further prospective validation.

This prospective cohort study tested whether baseline three-dimensional optical coherence tomography (OCT) and OCT angiography (OCTA) lesion volumes are associated with patient-reported visual function after anti-vascular endothelial growth factor (anti-VEGF) therapy in neovascular age-related macular degeneration (nAMD). Ninety-two treatment-na & iuml;ve nAMD eyes underwent volumetric segmentation of their baseline lesion components, including vascular subretinal hyper-reflective material (vSHRM), avascular subretinal hyper-reflective material (avSHRM), subretinal fluid, intraretinal fluid, and serous pigment epithelial detachment. The National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) was administered at the 2-year visit. Univariate standardized regressions across 36 biomarker-subscale pairs were corrected for multiple testing with the Benjamini-Hochberg false discovery rate (FDR). Three univariate associations survived FDR correction (q < 0.05). In multivariate analysis, baseline vSHRM volume was independently associated with a worse VFQ-25 composite score (standardized beta =-0.366, p = 0.001), and baseline avSHRM volume was independently associated with a worse near activities score (standardized beta = -0.370, p < 0.001), adding 8.0% and 11.9% incremental variance beyond clinical covariates. Baseline vSHRM and avSHRM volumes thus add prognostic information about patient-reported visual function beyond best-corrected visual acuity and clinical covariates. This study was registered in Chinese Clinical Trial Registry (www.chictr.org.cn/showproj.html?proj=173189; ID: ChiCTR2200063428; date of registration: 2022-09-06).

Purpose:To explore the choroidal vasculature changes in central serous chorioretinopathy (CSC) with symmetric and asymmetric choroidal venous drainage system using widefield optical coherence tomography angiography (WF-OCTA). Methods:In this retrospective study, choroidal characteristics were evaluated in CSC eyes through WF-OCTA. Eyes were classified based on choroidal venous drainage patterns: symmetric, one dominant vortex vein (DVV), and two DVV patterns. The location of DVVs was mapped to four quadrants: superotemporal, inferotemporal, superonasal, and inferonasal. Quantitative parameters including choroidal thickness (CT), choroidal volume (CV), choroidal vascularity index, and choriocapillaris flow density (CCFD) were analyzed both globally and within each quadrant. Results:Of 187 eyes from 146 patients, 43 eyes (22.99%) showed symmetric and 144 eyes (77.00%) demonstrated asymmetric choroidal venous drainage patterns. In the asymmetric cases, 78 eyes (41.71%) exhibited one-DVV and 66 eyes (35.29%) showed two-DVV patterns. One-DVV cases demonstrated significantly increased CT and CV, but decreased CCFD in DVV-related quadrants compared to symmetric cases (P < 0.05 for all), except for CCFD in cases with inferonasal-located DVV (P = 0.110). Moreover, when DVVs were located in superotemporal or superonasal quadrants, a significant reduction in overall CCFD was also observed (P = 0.010 and P = 0.021, respectively). In contrast, two-DVV cases exhibited predominant choroidal vascular alterations in the quadrants near the DVV locations. Overall CCFD was significantly lower in one-DVV cases (46.94% ± 1.30%) compared to two-DVV cases (47.92% ± 1.70%, P < 0.001). Conclusions:CSC eyes with asymmetric venous drainage demonstrated more significant choroidal alterations than symmetric cases, particularly when DVVs were located in superior quadrants. In contrast to one-DVV cases, two-DVV patterns showed more balanced choroidal circulation, likely through compensatory intervortex anastomoses. Translational Relevance:This study investigates the relationship between choroidal parameters and varying patterns of preferential choroidal venous drainage in CSC eyes, showing that CSC eyes with asymmetric pattern demonstrated more significant choroidal alterations than symmetric cases.

PURPOSE:To evaluate the choroidal vein distribution pattern in eyes with central serous chorioretinopathy (CSC) using widefield indocyanine green angiography (WF-ICGA) and widefield optical coherence tomography angiography (WF-OCTA). DESIGN:Retrospective, comparative validity and reliability analysis. SUBJECT:Patients diagnosed with CSC between September 2022 and September 2024. METHODS:WF-ICGA and WF-OCTA were performed to obtain widefield imaging. MAIN OUTCOME MEASURES:Choroidal venous drainage paths were classified as symmetry or asymmetry based on the presence of a dominant vein. In asymmetrically distributed eyes, the number and location of dominant vortex veins were recorded. Additionally, choroidal parameters were quantitatively assessed and compared among eyes with different choroidal vein distribution patterns. RESULTS:105 subjects were included in this study, with a mean age of 46.32 years, of whom 86 were male. In the 151 affected eyes, WF-ICGA and WF-OCTA detected similar rates of asymmetric distribution (76.82% vs. 78.14%, P = .783). The number and location of dominant vortex veins also showed no significant differences (P > .05 for all). WF-ICGA and WF-OCTA recognized the highest proportion of cases with 1 dominant vortex vein (43.71% and 49.01%, respectively), followed by cases with 2 dominant veins (33.11% and 29.14%, respectively), and finally, those with symmetric venous distribution (23.18% and 21.85%, respectively). The WF-OCTA results displayed strong agreement with WF-ICGA results (κ = 0.838, P < .001). Among the 21 cases (13.91%) with inconsistent results, the discrepancy was attributed to the limited nasal field of view in WF-OCTA (7 eyes), misidentification of choroidal venous anastomoses as dominant vortex veins (10 eyes), and poor vessel visualization on WF-OCTA (4 eyes). Compared to eyes with symmetric venous distribution and those with 2 dominant veins, cases with 1 dominant vortex vein exhibited worse visual acuity and lower choriocapillaris flow density (P = .009 and P = .008, respectively). CONCLUSIONS:WF-OCTA offers results comparable to WF-ICGA for assessing choroidal vein distribution patterns, establishing it as a reliable alternative for evaluating CSC choroidal vasculature.

PURPOSE:To explore the relationship between characteristics of macular neovascularisation (MNV) and photoreceptor integrity in patients with neovascular age-related macular degeneration (nAMD). METHODS:This prospective study enrolled treatment-naïve nAMD eyes and conducted a 3-month follow-up. 16 quantitative MNV features were evaluated using optical coherence tomography angiography, and the impaired areas of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL) were obtained using optical coherence tomography. Correlation and regression analyses assessed the relationships between MNV features and photoreceptor integrity. RESULTS:110 nAMD eyes from 110 patients (73.64% men) were included. Baseline MNV characteristics, including MNV perimeter, maxFeret, minFeret, vessel area, total vessel length, total number of junctions and endpoints, and mean E lacunarity, were positively correlated with photoreceptor damage areas (r ranging from 0.227 to 0.558, p<0.05 for all). Meanwhile, vessel density negatively correlated with photoreceptor damage (r=-0.468 for EZ, -0.394 for ELM and -0.538 for ONL, all p<0.05). After the loading phase, the EZ prognosis was independently associated with baseline MNV minFeret (Std β=0.362, p=0.011) and mean E lacunarity (Std β=0.130, p=0.041). The prognosis for ELM was independently linked to baseline MNV minFeret (Std β=0.373, p=0.014), while no significant factors were found to influence ONL prognosis (p>0.05 for all). CONCLUSION:A strong correlation was observed between MNV features and photoreceptor integrity, with larger and more complex vascular networks associated with greater photoreceptor damage.

PURPOSE:To explore the association between early response of different lesions and the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD). METHODS:This prospective study included treatment-naïve nAMD eyes with a 2-year follow-up period. Volumetric changes of multiple lesions during the loading phase were documented, including subretinal fluid (SRF), intraretinal fluid (IRF), vascular subretinal hyper-reflective material (vSHRM) and avascular subretinal hyper-reflective material, fibrovascular pigment epithelial detachment and serous pigment epithelial detachment (sPED) and total lesion. Imaging biomarkers associated with treatment frequency were analysed for 1-year and 2-year periods. RESULTS:A total of 92 eyes (92 patients) were included, with a mean age of 65.77±7.28 years. During the loading phase, all lesions except vSHRM showed significant temporal changes (p<0.05). Multivariate regression revealed that greater SRF changes at month 3 and IRF changes at month 1 were associated with increased injection frequency for both 1-year (β=0.353 and 0.360, p=0.025 and 0.022) and 2-year periods (β=0.336 and 0.293, p=0.004 and 0.026). Conversely, greater changes in vSHRM and sPED at month 2 were associated with fewer first-year injections (β=-0.307 and -0.697, p=0.023 and 0.022), while sPED changes at months 2 and 3 correlated with reduced 2-year requirements (β=-0.845 and -0.297, p=0.005 and 0.031). CONCLUSION:Enhanced absorption of SRF and IRF during early treatment was associated with increased injection frequency, while greater absorption of vSHRM and sPED correlated with reduced treatment requirements. TRIAL REGISTRATION NUMBER:ChiCTR2200063428.

Purpose:Identify optimal metabolic features and pathways across diabetic retinopathy (DR) stages, develop risk models to differentiate diabetic macular edema (DME), and predict anti-vascular endothelial growth factor (anti-VEGF) therapy response. Methods:We analyzed 108 aqueous humor samples from 78 type 2 diabetes mellitus patients and 30 healthy controls. Ultra-high-performance liquid chromatography-high-resolution-mass-spectrometry detected lipidomics and metabolomics profiles. DME patients received ≥3 anti-VEGF treatments, categorized into strong and weak response groups. Machine learning (ML) screened prospective metabolic features, developing prediction models. Results:Key metabolic features identified in the metabolomics and lipidomics datasets included n-acetyl isoleucine (odds ratio [OR] = 1.635), cis-aconitic acid (OR = 3.296), and ophthalmic acid (OR = 0.836) for DR. For early-DR, n-acetyl isoleucine (OR = 1.791) and decaethylene glycol (PEG-10) (OR = 0.170) were identified as key markers. L-kynurenine (OR = 0.875), niacinamide (OR = 0.843), and linoleoyl ethanolamine (OR = 0.941) were identified as significant indicators for DME. Trigonelline (OR = 1.441) and 4-methylcatechol-2-sulfate (OR = 1.121) emerged as predictors for strong response to anti-VEGF. Predictive models achieved R² values of 99.9%, 97.7%, 93.9%, and 98.4% for DR, early-DR, DME, and strong response groups in the calibration set, respectively, and validated well with R² values of 96.3%, 96.8%, 79.9%, and 96.3%. Conclusions:This research used ML to identify differential metabolic features from metabolomics and lipidomics datasets in DR patients. It implies that metabolic indicators can effectively predict early disease progression and potential weak responders to anti-VEGF therapy in DME eyes. Translational Relevance:The identified metabolic indicators may aid in predicting the early progression of DR and optimizing therapeutic strategies for DME.

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.

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 (β = 0.377, P < 0.001), avascular SHRM (β = 0.306, P = 0.032), and ELM impairment area (β = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (β = 0.374, p = 0.003; β = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (β = 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.

PURPOSE:This study aimed to elucidate the distribution and morphological features of choroidal vortex veins in pachychoroid disease (PCD). DESIGN:Retrospective observational study. SUBJECTS:Patients with PCD included from January 2022 to June 2023. METHODS:We conducted a retrospective cross-sectional analysis using wide-field indocyanine green angiography (WF-ICGA) to assess choroidal vortex veins in PCD patients, categorizing them based on location (equatorial/posterior) and morphology (absent, incomplete, complete, complete with ampulla). MAIN OUTCOME MEASURES:The incidence of different location and morphology of vortex veins in PCD. RESULTS:A total of 190 eyes from 99 PCD patients were examined. Notably, only 8.9 % (17/190) of eyes had posterior vortex veins. We identified 1620 vortex veins, predominantly equatorial (99 %, 1603/1620). Morphologically, the most common type was incomplete (61.9 %), followed by complete (19.5 %), absent (11.1 %), and complete with ampulla (7.5 %). The distribution of these veins varied, with the inferotemporal quadrant showing the highest prevalence at 26.9 %, followed by the superonasal (26.1 %), superotemporal (24.3 %), and inferonasal (22.7 %) quadrants. The median number of vortex veins per eye was 8, with a range from 5 to 15. CONCLUSIONS:This study highlights that posterior vortex veins are less frequent in PCD eyes, with incomplete veins being the most prevalent. These findings provide important clinical evidence for understanding the distribution and morphologic characteristics of choroidal vortex veins in PCD, contributing to our knowledge of the pathophysiological mechanisms underlying this condition.

Purpose: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements. Methods: In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas. Results: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material. Conclusions: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

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.

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.

PURPOSE:To report the novel imaging findings in persistent placoid maculopathy (PPM) from the first case series of Asian subjects. DESIGN:Retrospective observational case series. SUBJECTS:Patients with PPM from 2013 to 2023. METHODS:Medical records and multimodal images from each visit were analyzed. MAIN OUTCOME MEASURES:Imaging and follow-up findings. RESULTS:Twenty-one eyes of 16 patients were included. Mean age was 61 (range, 48-84) years old. Five patients showed bilateral involvement. Persistent placoid maculopathy lesions were unremarkable on color fundus photography, autofluorescence, and fluorescein angiography. Hypofluorescent spots with a lichen-like appearance presented in all phases of indocyanine green angiography, which were most prominent in the late phase and presented in a fused (71%) or clustered (29%) pattern. The hypofluorescence correlated with the lesions between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) with moderate reflectivity on OCT, and the thickness ranged from slit-like to mound-like. The intensity of hypofluorescence sometimes varied in the same eye and correlated with the thickness of sub-RPE lesions on OCT. No abnormal blood flow signals were detected in either the sub-RPE space or choriocapillaris slab of OCT angiography across the PPM lesions. Peripapillary (5 eyes, 24%) and extra posterior pole (2 eyes, 10%) involvements were seen, the former sparing the β zones of optic discs. Ten eyes of 7 patients were followed up (median, 26 months; range, 2-121 months). During follow-up, the lichen-like lesions spread and migrated slowly without changing the plane patterns of the first visit and were limited to sub-RPE growth. The fused lichen-like pattern sprawled around the enlarged base. The clustered lichen-like pattern gradually loosened. Ten eyes (48%, 9 eyes in the fused pattern, 1 eye in the clustered pattern) had secondary choroidal neovascularization (CNV) at the first visit, with type I (6 eyes, 5 of which were polypoidal choroidal vasculopathy) and type II (4 eyes). No new CNV developed during follow-up. CONCLUSION:Persistent placoid maculopathy lesions were located in the sub-RPE space, as determined by multimodal imaging. Spreading and migration between the RPE and BM may account for their unique lichen-like appearance and progression pattern. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

Purpose: To determine the expression levels of SIRT6 and NMNAT2 in diabetic retinopathy (DR).Methods: We obtained peripheral blood mononuclear cells (PBMCs) and vitreous samples from 77 patients with type 2 diabetes mellitus: 52 with DR and 25 without DR, and 27 healthy control subjects. Western blot analysis and qRT-PCR were performed to evaluate the expression of SIRT6 and NMNAT2 in their PBMCs. The levels of IL-1 beta, IL-6, and TNF-alpha in the vitreous fluid were determined by ELISA. Immunohistochemistry was performed to detect the expression of SIRT6 and NMNAT2 in proliferative DR (PDR) and the control subjects.Results: The expression of SIRT6 and NMNAT2 was markedly downregulated in DR patients, which was negatively correlated with the increased expression of IL-1 beta, IL-6 and TNF-alpha. Additionally, we observed decreased expression of SIRT6 and NMNAT2 in the fibrovascular membranes of PDR patients.Conclusions: The downregulated expression of SIRT6 and NMNAT2 in PDR patients reveals a potential pathogenic association; more extended studies could verify them as potential therapeutic targets.

To correlate the hyperfluorescent lines in the peripheral fundus on late-phase indocyanine green angiography (ICGA) to infrared and optical coherence tomography (OCT) findings. This is a retrospective, cross-sectional study. Multimodal imaging data, including ICGA, fluorescein angiography, infrared imaging, and OCT were analyzed. The hyperfluorescent lines were categorized into 2 grades according to their extents. In addition, serum levels of apolipoprotein (Apo) A and B were measured by enzyme linked immunosorbent assay. A total of 247 patients who underwent multimodal imaging were reviewed. The hyperfluorescent lines in the peripheral fundus on late-phase ICGA were detected in 96 patients, and were correlated to superficial choroidal arteries by infrared imaging and OCT. The incidence of hyperfluorescent choroidal arteries in the peripheral fundus (HCAP) on late-phase ICGA increased in groups of older ages (0–20 years, 4.3%; 20–40 years, 2.6%; 40–60 years, 48.9%; >60 years, 88.7%; p < 0.001). In addition, the mean age increased with the grades of HCAP (grade 1, 52.3 ± 10.8 years; grade 2, 63.3 ± 10.5 years; p < 0.001). The hyperfluorescence was also detected in posterior choroidal arteries in 11 eyes, all patients in grade 2. There was no significant correlation between grades of HCAP and gender, or serum level of ApoA and ApoB. The occurrence and grades of HCAP increased with age. The superficial location of choroidal arteries in the peripheral fundus exposes their hyperfluorescence on late-phase ICGA. HCAP might reveal the local lipid degeneration of choroidal artery walls, according to ICG binding properties.

Purpose This study aimed to evaluate serum lutein and zeaxanthin levels and macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC). Methods Fifty-four patients with acute CSC (28–56 years old; 44 men and 10 women) and 62 matched controls were enrolled. Serum lutein and zeaxanthin were measured using the high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method. MPOD was measured at 7° of eccentricity and reported in parameters as “max” and “mean” optical density (OD) (Visucam 200; Carl Zeiss Meditec). MPOD was re-measured in 9 patients whose subretinal fluid was absorbed. Results The average max OD and the mean OD in CSC were 0.275 ± 0.047 d.u. and 0.098 ± 0.018 d.u., respectively, which were significantly lower than the control (p < 0.001). The average MPOD value in the unaffected eyes of patients with CSC was 0.298 ± 0.045 for max OD, 0.106 ± 0.017 for mean OD, and both were significantly lower compared with the affected eyes (p < 0.001 for max OD, p = 0.01 for mean OD). In the 9 follow-up patients, the decrease in MPOD was partially recovered. The mean serum level was 409.80 ± 182.52 ng/ml for lutein and 22.97 ± 12.23 ng/ml for zeaxanthin in patients with CSC. In controls, the mean serum level was 393.38 ± 202.44 ng/ml for lutein and 22.16 ± 10.12 ng/ml for zeaxanthin. The difference was not statistically significant (p = 0.649, p = 0.698, respectively). Conclusion MPOD decreased within 7° of eccentricity in CSC without serum lutein and zeaxanthin changes. The decrease may be due to the subretinal fluid. Whether local oxidative stress is involved in CSC and the supplementation with lutein and zeaxanthin is helpful for CSC requires further investigation.

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.