DrugMap: A quantitative pan-cancer analysis of cysteine ligandability.

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors for a wide range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed "DrugMap," an atlas of cysteine ligandability compiled across 416 cancer cell lines. We unexpectedly find that cysteine ligandability varies across cancer cell lines, and we attribute this to differences in cellular redox states, protein conformational changes, and genetic mutations. Leveraging these findings, we identify actionable cysteines in NF-κB1 and SOX10 and develop corresponding covalent ligands that block the activity of these transcription factors. We demonstrate that the NF-κB1 probe blocks DNA binding, whereas the SOX10 ligand increases SOX10-SOX10 interactions and disrupts melanoma transcriptional signaling. Our findings reveal heterogeneity in cysteine ligandability across cancers, pinpoint cell-intrinsic features driving cysteine targeting, and illustrate the use of covalent probes to disrupt oncogenic transcription-factor activity.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability.

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors of a wide-range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed DrugMap , an atlas of cysteine ligandability compiled across 416 cancer cell lines. We unexpectedly find that cysteine ligandability varies across cancer cell lines, and we attribute this to differences in cellular redox states, protein conformational changes, and genetic mutations. Leveraging these findings, we identify actionable cysteines in NFκB1 and SOX10 and develop corresponding covalent ligands that block the activity of these transcription factors. We demonstrate that the NFκB1 probe blocks DNA binding, whereas the SOX10 ligand increases SOX10-SOX10 interactions and disrupts melanoma transcriptional signaling. Our findings reveal heterogeneity in cysteine ligandability across cancers, pinpoint cell-intrinsic features driving cysteine targeting, and illustrate the use of covalent probes to disrupt oncogenic transcription factor activity.

A multi-omics analysis reveals that the lysine deacetylase ABHD14B influences glucose metabolism in mammals.

The sirtuins and histone deacetylases are the best characterized members of the lysine deacetylase (KDAC) enzyme family. Recently, we annotated the "orphan" enzyme ABHD14B (α/ß-hydrolase domain containing protein # 14B) as a novel KDAC and showed this enzyme's ability to transfer an acetyl-group from protein lysine residue(s) to coenzyme-A to yield acetyl-coenzyme-A, thereby, expanding the repertoire of this enzyme family. However, the role of ABHD14B in metabolic processes is not fully elucidated. Here, we investigated the role of this enzyme using mammalian cell knockdowns in a combined transcriptomics and metabolomics analysis. We found from these complementary experiments in vivo that the loss of ABHD14B results in significantly altered glucose metabolism, specifically the decreased flux of glucose through glycolysis and the citric acid cycle. Further, we show that depleting hepatic ABHD14B in mice also results in defective systemic glucose metabolism, particularly during fasting. Taken together, our findings illuminate the important metabolic functions that the KDAC ABHD14B plays in mammalian physiology and poses new questions regarding the role of this hitherto cryptic metabolism-regulating enzyme.

Mycobacterium tuberculosis Transcription Factor EmbR Regulates the Expression of Key Virulence Factors That Aid in Ex Vivo and In Vivo Survival.

Mycobacterium tuberculosis encodes ~200 transcription factors that modulate gene expression under different microenvironments in the host. Even though high-throughput chromatin immunoprecipitation sequencing and transcriptome sequencing (RNA-seq) studies have identified the regulatory network for ~80% of transcription factors, many transcription factors remain uncharacterized. EmbR is one such transcription factor whose in vivo regulon and biological function are yet to be elucidated. Previous in vitro studies suggested that phosphorylation of EmbR by PknH upregulates the embCAB operon. Using a gene replacement mutant of embR, we investigated its role in modulating cellular morphology, antibiotic resistance, and survival in the host. Contrary to the prevailing hypothesis, under normal growth conditions, EmbR is neither phosphorylated nor impacted by ethambutol resistance through the regulation of the embCAB operon. The embR deletion mutant displayed attenuated M. tuberculosis survival in vivo. RNA-seq analysis suggested that EmbR regulates operons involved in the secretion pathway, lipid metabolism, virulence, and hypoxia, including well-known hypoxia-inducible genes devS and hspX. Lipidome analysis revealed that EmbR modulates levels of all lysophospholipids, several phospholipids, and M. tuberculosis-specific lipids, which is more pronounced under hypoxic conditions. We found that the EmbR mutant is hypersusceptible to hypoxic stress, and RNA sequencing performed under hypoxic conditions indicated that EmbR majorly regulates genes involved in response to acidic pH, hypoxia, and fatty acid metabolism. We observed condition-specific phosphorylation of EmbR, which contributes to EmbR-mediated transcription of several essential genes, ensuring enhanced survival. Collectively, the study establishes EmbR as a key modulator of hypoxic response that facilitates mycobacterial survival in the host. IMPORTANCE Mycobacterium tuberculosis modulates its transcriptional machinery in response to dynamic microenvironments encountered within the host. In this study, we identified that EmbR, a transcription factor, plays important roles in modulating cellular morphology, antibiotic resistance, and survival in the host. We found that EmbR undergoes condition-specific phosphorylation for its activation. Together, the study establishes a key role of EmbR as a transcriptional activator of genes belonging to multiple pathways, viz., virulence, secretion, or polyketide synthesis, that aid in mycobacterial survival during hypoxia and within the host.

Fatty acid chain length drives lysophosphatidylserine-dependent immunological outputs.

In humans, lysophosphatidylserines (lyso-PSs) are potent lipid regulators of important immunological processes. Given their structural diversity and commercial paucity, here we report the synthesis of methyl esters of lyso-PS (Me-lyso-PSs) containing medium- to very-long-chain (VLC) lipid tails. We show that Me-lyso-PSs are excellent substrates for the lyso-PS lipase ABHD12, and that these synthetic lipids are acted upon by cellular carboxylesterases to produce lyso-PSs. Next, in macrophages we demonstrate that VLC lyso-PSs orchestrate pro-inflammatory responses and in turn neuroinflammation via a Toll-like receptor 2 (TLR2)-dependent pathway. We also show that long-chain (LC) lyso-PSs robustly induce intracellular cyclic AMP production, cytosolic calcium influx, and phosphorylation of the nodal extracellular signal-regulated kinase to regulate macrophage activation via a TLR2-independent pathway. Finally, we report that LC lyso-PSs potently elicit histamine release during the mast cell degranulation process, and that ABHD12 is the major lyso-PS lipase in these immune cells.

Superspreaders: A Lurking Danger in the Community.

A "superspreader" refers to an unusually contagious organism infected with a disease. With respect to a human borne illnesses, a superspreader is someone who is more likely to infect other humans when compared to a typically infected person. The existence of human superspreaders is deeply entrenched in history; the most famous case being that of Typhoid Mary. Through contact tracing, epidemiologists have identified human superspreaders in measles, tuberculosis, rubella, monkeypox, smallpox, Ebola hemorrhagic fever, and SARS. The recent outbreak of Coronavirus disease (COVID-19) has shifted the focus back on the superspreaders. We herein present a case report of a COVID-19 superspreader with a hitherto unusually high number of infected contacts. The index case was a 33 year old male who resided in a low income settlement comprising of rehabilitated slum dwellers and worked as a healthcare worker (HCW) in a tertiary care hospital and had tested positive for COVID-19.On contact tracing, he had a total of 125 contacts, of which 49 COVID-19 infections had direct or indirect contact with the index case, qualifying him as a "superspreader." This propagated infection led to an outbreak in the community. Contact tracing, testing and isolation of such superspreaders from the other members of the community is essential to stop the spread of this disease and contain the COVID-19 pandemic.

Choroidal Structural Changes in Patients with Birdshot Chorioretinopathy.

Purpose: To assess the choroidal vascularity index (CVI) in birdshot chorioretinopathy (BSCR) patients.Methods: The CVI was calculated as the ratio of luminar area to the total subfoveal choroidal area on enhanced-depth imaging optical coherence tomography. Intraocular inflammation was defined by the presence of macular edema and/or vitritis and/or vasculitis and/or papillitis.Results: Eighty BSCR patients and 22 healthy controls were included. Foveal choroidal thickness was lower in the BSCR compared with the control group (p < 0.001). CVI was not different between the two groups. CVI was significantly higher in BSCR patients with inflammatory activity (p = 0.004). Using a multivariate linear regression model, longer disease duration was associated with lower CVI (p = 0.038), whereas the presence of papillitis was associated with a higher CVI (p = 0.003).Conclusions: The CVI was not different between the BSCR and the control group. However, the CVI may be used as a new tool for monitoring inflammatory activity in BSCR.

The Lysophosphatidylserines-An Emerging Class of Signalling Lysophospholipids.

Lysophospholipids are potent hormone-like signalling biological lipids that regulate many important biological processes in mammals (including humans). Lysophosphatidic acid and sphingosine-1-phosphate represent the best studied examples for this lipid class, and their metabolic enzymes and/or cognate receptors are currently under clinical investigation for treatment of various neurological and autoimmune diseases in humans. Over the past two decades, the lysophsophatidylserines (lyso-PSs) have emerged as yet another biologically important lysophospholipid, and deregulation in its metabolism has been linked to various human pathophysiological conditions. Despite its recent emergence, an exhaustive review summarizing recent advances on lyso-PSs and the biological pathways that this bioactive lysophospholipid regulates has been lacking. To address this, here, we summarize studies that led to the discovery of lyso-PS as a potent signalling biomolecule, and discuss the structure, its detection in biological systems, and the biodistribution of this lysophospholipid in various mammalian systems. Further, we describe in detail the enzymatic pathways that are involved in the biosynthesis and degradation of this lipid and the putative lyso-PS receptors reported in the literature. Finally, we discuss the various biological pathways directly regulated by lyso-PSs in mammals and prospect new questions for this still emerging biomedically important signalling lysophospholipid.

Normal aging changes in the choroidal angioarchitecture of the macula.

The choroidal vascularity index (CVI) has been shown to be sensitive in detecting changes in choroidal angioarchitecture in a range of ocular diseases. However, changes in CVI in association with normal physiological aging and spatial distribution remains to be determined. This is significant as a range of ocular conditions with choroidal degeneration are associated with aging. In this study, we assessed CVI for 106 healthy eyes from 106 individuals (range 21-78 years old, ~ 20 individuals/decade) at 15 eccentricities across the macula (0, 230 µm, 460 µm, 690 µm, 1,150 µm, 1,380 µm and 2,760 µm from the fovea in the superior and inferior direction). Total choroidal area, luminal area and stromal area were all significantly decreased with age (p < 0.001 for all parameters). CVI was also significantly decreased with age (p < 0.01) and eccentricity. Fitting of quadratic regression curves to CVI as a function of age yielded a good fit for all eccentricities (r2 = 0.55-0.80) and suggested a decrease in CVI from the ages of 33-43 years at a rate of 0.7-2.7% per decade. CVI was lower in the inferior versus superior retina at matching eccentricities and a significant difference in age-related decline of CVI with eccentricity only occurred in inferior locations. These findings suggest choroidal angioarchitecture declines from the 4th decade of life with potential eccentricity differences in the inferior and superior retina. Considering the number of age-related diseases with choroidal dysfunction, these results provide foundational knowledge to understand choroidal involvement in these diseases.

Choroidal structural changes in preterm children with and without retinopathy of prematurity.

PURPOSE: Evaluate choroidal structural changes in preterm children with and without retinopathy of prematurity (ROP) using image binarization technique on swept-source optical coherence tomography (SS-OCT) scans. METHODS: Prospective case-control study. Forty-one (79 eyes) children aged 5-15 years with a history of preterm birth and 33 (63 eyes) age-matched full-term children were recruited. Demographics including gestational age at birth, birth weight and history of ROP were documented. All subjects had undergone complete eye examinations, including best-corrected visual acuity and SS-OCT imaging. Subfoveal choroidal thickness (SFCT) was calculated, and images were binarized to obtain stromal and luminal areas (LA). The choroidal vascularity index (CVI) was derived from the proportion of LA to the total subfoveal choroidal area. RESULTS: There were no significant differences in SFCT between the preterm children with (286.63 ± 83.98 µm) or without (306.59 ± 77.29 µm) ROP and the full-term children (311.82 ± 42.87; p = 0.20 and 0.67, respectively). The CVI was significantly reduced in the preterm children with ROP (68.66 ± 3.24%; p = 0.005) compared with the CVI in the full-term control group (71.37 ± 3.63%); however, the CVI in the preterm children without ROP (71.68 ± 3.09%; p = 0.93) was not significantly affected. CONCLUSION: The reduced CVI in preterm children with ROP may indicate compromised choroidal vascularity. The CVI was found to be a more sensitive OCT biomarker than the SFCT and may be helpful in evaluating associated choroidal structural changes in preterm children, especially those with a history of ROP.

Fluorescein Labeled Leukocytes for in vivo Imaging of Retinal Vascular Inflammation and Infiltrating Leukocytes in Laser-Induced Choroidal Neovascularization Model.

Purpose: To study the effect of anti-VEGF treatment on retinal inflammation in a laser-induced CNV rodent model.Methods: Leukocytes labeled with 1% sodium fluorescein were injected into the laser-induced CNV (wild type C57BL/6) mice at days 4 (baseline), 7, 14, and 19. At baseline intravitreally 3 mice received 1× PBS, and 3 mice received anti-VEGF. FFA, OCT, and SLO were performed at each time point to assess the CNV pathophysiology and inflammatory response.Results: Fluorescein leakage, SRF, and leukocyte infiltration were observed at baseline in both the groups before injection. From days 7 to 19, leukocyte infiltration and SRF were noted in the 1× PBS group, but limited or no SRF and leukocyte infiltration was observed in the anti-VEGF group.Conclusions: Leukocyte infiltration was established as an in vivo imaging inflammatory marker and along with FFA and OCT showed response to anti-VEGF therapy in laser-induced CNV model.

Peripapillary Choroidal Vascularity Index and Microstructure of Parapapillary Atrophy.

Purpose: To investigate the association between the microstructure of ß-zone parapapillary atrophy (ßPPA) and choroidal vascularity index (CVI) determined by spectral-domain optical coherence tomography (SD-OCT) in glaucomatous eyes. Methods: A total of 160 eyes of 160 primary open-angle glaucoma patients with ßPPA were included. Total choroidal area (TCA), luminal area (LA), and CVI were measured at a 3.5-mm distance from the Bruch's membrane (BM) opening center by image binarization of SD-OCT B-scans. The widths of ßPPA with BM (ßPPA+BM) and without BM (ßPPA-BM), and juxtapapillary choroidal thickness (JPCT) were measured on six radial SD-OCT images. OCT angiography-derived parapapillary deep-layer microvasculature dropout (MvD_P) was also derived. Results: In the multivariate regression analysis, larger ßPPA+BM was significantly associated with smaller TCA and smaller LA (P < 0.05, respectively), but not with CVI and JPCT (P > 0.05, respectively). Meanwhile, ßPPA-BM was not significantly associated with TCA, LA, CVI, or JPCT in the multivariate regression analysis (P > 0.05). Conclusions: Despite significant relationship between the choroidal thinning and larger ßPPA+BM, choroidal vascularity was not associated with the ßPPA+BM width. These findings suggest that the presumed common pathogenic mechanism between RPE atrophy and peripapillary choroidal thinning may not be mediated by the impaired choroidal perfusion in glaucomatous eyes. Future studies on the mechanisms in explaining the relationship between the atrophy of retinal pigment epithelium (RPE) and choroid in glaucoma are needed.

Choroidal Structural Changes in Smokers Measured Using Choroidal Vascularity Index.

Purpose: Cigarette smoking is a known risk factor for vascular dysfunction. This study evaluated choroidal structural changes in smokers using the choroidal vascularity index (CVI) derived from image binarization on spectral domain optical coherence tomography scans with enhanced depth imaging (EDI-OCT). Methods: This cross-sectional study included 39 smokers and 44 non-smokers. Choroidal images on EDI-OCT were binarized into luminal area (LA) and stromal area (LA). CVI was calculated as the ratio of LA to total choroid area (TCA). CVI, foveal retinal thickness (FRT), and subfoveal choroidal thickness (SFCT) between smokers and non-smokers were compared using likelihood ratio test with linear mixed model. Trend and subgroup analysis were performed to investigate the dose-dependent relationship between CVI/FRT/SFCT and pack-years. Results: CVI in smokers (65 ± 2%) was lower compared to non-smokers (67 ± 2%, P = 0.0001). The difference remained significant after adjusting for age (P = 0.001). There was no significant association between cigarette smoking and FRT/SFCT. CVI decreased by 0.12% with each unit increase in smoking measured by pack-year (P = 0.0009). In subgroup analysis, those who smoked 8 to 12 and >12 pack-years had significantly lower CVI compared to non-smokers (both P < 0.05). Conclusions: Cigarette smoking is associated with decreased choroidal vascularity in healthy subjects, and this association appears to be dose dependent. CVI might be a non-invasive marker of vascular health in smokers.

Vascular Response to Sildenafil Citrate in Aging and Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) - the leading cause of vision loss in the elderly - share many risks factors as atherosclerosis, which exhibits loss of vascular compliance resulting from aging and oxidative stress. Here, we attempt to explore choroidal and retinal vascular compliance in patients with AMD by evaluating dynamic vascular changes using live ocular imaging following treatment with oral sildenafil citrate, a phosphodiesterase type 5 (PDE5) inhibitor and potent vasodilator. Enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A) were performed on 46 eyes of 23 subjects, including 15 patients with non-exudative AMD in one eye and exudative AMD in the fellow eye, and 8 age-matched control subjects. Choroidal thickness, choroidal vascularity, and retinal vessel density were measured across the central macula at 1 and 3 hours after a 100 mg oral dose of sildenafil citrate. Baseline choroidal thickness was 172.1 ± 60.0 µm in non-exudative AMD eyes, 196.4 ± 89.8 µm in exudative AMD eyes, and 207.4 ± 77.7 µm in control eyes, with no difference between the 3 groups (P = 0.116). After sildenafil, choroidal thickness increased by 6.0% to 9.0% at 1 and 3 hours in all groups (P = 0.001-0.014). Eyes from older subjects were associated with choroidal thinning at baseline (P = 0.005) and showed less choroidal expansion at 1 hour and 3 hours after sildenafil (P = 0.001) regardless of AMD status (P = 0.666). The choroidal thickening appeared to be primarily attributed to expansion of the stroma rather than luminal component. Retinal vascular density remained unchanged after sildenafil in all 3 groups (P = 0.281-0.587). Together, our studies suggest that vascular response of the choroid to sildenafil decreases with age, but is not affected by the presence of non-exudative or exudative AMD, providing insight into changes in vessel compliance in aging and AMD.

Choroidal and Retinal Anatomical Responses Following Systemic Corticosteroid Therapy in Vogt-Koyanagi-Harada Disease Using Swept-Source Optical Coherence Tomography.

PURPOSE: To assess structural changes in retina and choroid after systemic corticosteroid therapy in Vogt-Koyanagi-Harada (VKH) disease using swept-source optical coherence tomography (SS-OCT). METHODS: SS-OCT was conducted before treatment and during first-month follow-up in 16 eyes treated with systemic corticosteroids for active VKH. Retina was divided into five zones depending on pretreatment choroidal thickness (CT) of <100, >100 to <200, >200 to <300, >300 to <400 and >400µm, and changes in retinal thickness and CT after treatment in these zones were compared with baseline. RESULTS: Mean CT significantly improved from 83.1±8.75 to 156.4±62.73µm(p = 0.008) in the zone with pre-CT <100µm and significantly decreased from 336.1 ± 17.28 to 266.28 ± 81.39µm(p = 0.008) in the zone with pre-CT > 300µm. CONCLUSIONS: We have shown choroidal remodeling in VKH. SS-OCT can serve as an important noninvasive tool in assessment of treatment response in patients with VKH disease.

FRACTAL DIMENSION AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF THE CENTRAL MACULA AFTER REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: Patients with macula-off rhegmatogenous retinal detachments (RRDs) may have suboptimal visual recovery, despite successful reattachment due to various reasons. This study was performed to evaluate the retinal microvasculature in subjects undergoing surgery for RRD using optical coherence tomography angiography. METHODS: In this case-control study, the analysis of optical coherence tomography angiography findings of 19 eyes of 19 patients (15 men) who underwent RRD surgery at a tertiary institute were compared with 19 eyes of 19 age- and sex-matched healthy subjects with no known ocular disease. 3 × 3-mm optical coherence tomography angiography scans were obtained at 3 months postoperatively and analyzed. Optical coherence tomography angiography images of patients with RRD and control subjects were analyzed for capillary density index and fractal dimensions. RESULTS: Mean age of the patients was 40.21 years, and the mean age of controls was 43.73 years. Eight eyes underwent scleral buckling alone, and 11 eyes underwent primary vitrectomy with gas tamponade (C3F8 gas) for macula-off RRD. None of the eyes had redetachment during the follow-up at 3 months. Mean capillary density index among patients was 33.28% ± 0.99% and 34.06% ± 2.22% in the superficial and deep retinal plexuses, respectively, compared with 36.11% ± 1.29% and 37.52% ± 1.24% among controls (P < 0.001). The mean fractal dimension was lower among subjects compared with controls (1.46 vs. 1.61 in the superficial plexus, P < 0.001; 1.58 vs. 1.64 in the deep plexus, P < 0.001). CONCLUSION: Optical coherence tomography angiography demonstrates significant reduction in mean capillary density index and fractal dimension in patients after surgery for RRD in our patients. Thus, reduction in vascular perfusion and branching pattern identified using novel analysis techniques on optical coherence tomography angiography images may provide an insight into the reasons for suboptimal visual gain after RRD surgery.

Choroidal structural analysis and vascularity index in retinal dystrophies.

PURPOSE: To assess choroidal structural changes in patients with retinal dystrophies using choroidal vascularity index (CVI), a novel optical coherence tomography (OCT) based tool. METHODS: This retrospective study included 26 patients with retinal dystrophies (17 with retinitis pigmentosa, four with Stargardt disease, three with cone-rod dystrophy, one each with Best disease and Bietti crystalline dystrophy) and 32 healthy controls. Subfoveal OCT images were used for analysis. Mean CVI was compared between retinal dystrophy and control group, as well as among the retinal dystrophy subgroups. RESULTS: Mean CVI in eyes with retinal dystrophies was 52 ± 9% and it was significantly lower compared to that in normal eyes (70 ± 3%, p < 0.001). The differences among subgroups of retinal dystrophy were not statistically significant (p = 0.084). All types of retinal dystrophy were associated with lower CVI (all p < 0.001), after adjusting for age, gender, visual acuity and duration of symptoms. Older age was also shown to be independently associated with lower CVI (p = 0.012). Gender, visual acuity (VA) and duration of symptoms did not significantly affect CVI. CONCLUSION: Decreased choroidal vascularity was seen in eyes with retinal dystrophies. (CVI) may be a helpful tool in monitoring choroidal involvement in retinal dystrophies.

Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema-A novel OCT based imaging biomarker.

PURPOSE: To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans. METHODS: A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey's test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis. RESULTS: SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81µm vs 284.53±56.45µm, p<0.001), and showed an ascending trend with worsening of DR, though this difference was not statistically significant [mild non-proliferative diabetic retinopathy (NPDR) = 304.33±40.39µm, moderate NPDR = 327.81±47.39µm, severe NPDR = 357.72±62.65µm, proliferative DR (PDR) = 334.59±47.4µm, p-0.09]. CVI was significantly decreased in DME with DR eyes as compared to controls (63.89±1.89 vs 67.51±2.86, p<0.001). CVI was also significantly decreased with worsening DR (mild NPDR = 66.38±0.3, moderate NPDR = 65.28±0.37, severe NPDR = 63.50±0.47, PDR = 61.27±0.9, p<0.001). CONCLUSION: SFCT and CVI are dynamic parameters that are affected by DME. Unlike CVI, SFCT is also affected by ocular and systemic factors like edema and hypertension. CVI may be a more accurate surrogate marker for DME and DR and can potentially be used to monitor the progression of DR.

Peripapillary Choroidal Vascularity Index in Glaucoma-A Comparison Between Spectral-Domain OCT and OCT Angiography.

Purpose: To compare the choroidal vascularity index (CVI) determined by spectral-domain optical coherence tomography (OCT) between eyes with and without parapapillary deep-layer microvasculature dropout (MvD_P) assessed by OCT angiography in glaucomatous eyes. Methods: A total of 100 open-angle glaucoma patients with and without MvD_P (50 eyes of 50 patients in each group) matched by age and visual field mean deviation were included. Total choroidal area (TCA) and CVI were measured by image binarization of spectral-domain OCT B-scans in order to assess the choroidal vasculature outside ß-zone parapapillary atrophy (ßPPA) at a 3.5-mm distance from the Bruch's membrane opening center. MvD_P was determined by OCT angiography as a deep-layer microvasculature dropout within ßPPA. Global and sectoral (six 60° sectors) TCA and CVI were compared between eyes with and without MvD_P. Results: The CVIs of eyes with MvD_P were significantly lower than those without MvD_P, globally (P = 0.010) as well as in the inferotemporal (TI) (P = 0.003), temporal (P = 0.009), and nasal (P = 0.048) sectors. Eyes with MvD_P, of which the largest portion was located only in the TI sector (n = 33), had significantly lower CVI than those without MvD_P in the corresponding TI and temporal sectors (P < 0.05 for all), whereas TCA did not differ in any areas. Conclusions: Eyes with MvD_P had significantly lower CVIs than did those without MvD_P. Furthermore, CVI reduction was spatially correlated with MvD_P. Further studies investigating the influence of MvD_P on the choroidal vasculature outside ßPPA are warranted.

Choroidal vascularity index changes after vitreomacular surgery.

PURPOSE: To study the structural changes in the choroid using swept-source (SS) optical coherence tomography (OCT), a tool for the choroidal vascularity index (CVI) following epiretinal membrane removal. METHODS: Fifty-two eyes of 26 patients were evaluated in this prospective, single-centre, observational study. Twenty-six eyes underwent vitrectomy for epiretinal membrane removal (VT-group), and the control group consisted of 26 corresponding fellow eyes (F-group). All patients were evaluated at baseline, 30 and 90 days postsurgery. Using a modified image binarization algorithm for SS-OCT scans, the subfoveal choroidal area was segmented into the luminal and stromal areas, and the CVI was measured by calculating the proportion of the luminal area (LA) to the cross-sectional choroid area. RESULTS: The mean CVI in the VT-group was 63.86 ± 4.04% at the baseline, 62.45 ± 4.21% at 30 days postsurgery and 61.06 ± 3.79% at 90 days (p < 0.001). The F-group had a mean CVI of 61.12 ± 2.29% at the baseline, 60.91 ± 2.25% at 30 days postsurgery and 61.05 ± 2.28% at 90 days (p = 0.29). CONCLUSION: The CVI decreases following epiretinal membrane removal when compared to the fellow eyes, which suggests structural changes in the vascular layers of the choroid. The implication of these results may be that secondary inflammation resulting from mechanical traction induces choroidal thickness by way of increased vascularization of the choroid.