Untargeted metabolomic analysis of aqueous humor in diabetic macular edema.

Background: The mechanism of diabetic macular edema (DME) was explored by comparing the intraocular metabolite profiles of the aqueous humor of patients with DME to those of diabetic patients without DME using untargeted metabolomic analysis. Methods: Aqueous samples from 18 type 2 diabetic patients with DME and 18 type 2 diabetic patients without DME used as controls were analyzed using liquid chromatography-mass spectrometry (LCMS). The two groups of patients were age and gender matched and had no systemic diseases other than diabetes mellitus (DM). The metabolites were analyzed using orthogonal partial least square discriminant analysis. Results: The metabolite profiles in DME patients differed from those in DM controls. This indicates the following metabolic derangements in DME: (a) a higher amount of oxidized fatty acids but a lower amount of endogenous antioxidants (oxidative stress); (b) higher levels of ß-glucose and homocysteine but a lower level of sorbitol (hyperglycemia); (c) a higher amount of prostaglandin metabolites (inflammation); (d) higher amounts of acylcarnitines, odd-numbered fatty acids, and 7,8-diaminononanoate (respiration deterioration); (e) a higher amount of neurotransmitter metabolites and homovanillic acid (neuronal damage); (f) a lower amount of extracellular matrix (ECM) constituents (ECM deterioration); and (g) a higher amount of di-amino peptides (microvascular damage). Conclusions: The change in the metabolic profiles in the aqueous humor of DME patients compared to DM controls without DME indicates that DME patients may have less capability to resist various stresses or damaging pathological conditions, such as oxidative stress, mitochondrial insufficiency, inflammation, and ECM deterioration.

Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation.

Angiopoietin 2 (ANG2) is a proangiogenic cytokine which may have an implication in neovascular age related macular degeneration (nAMD). In 24 eyes of 24 subjects presenting with treatment naïve nAMD and 26 eyes of 26 control patients, aqueous humor samples were collected at the time of intervention (intravitreal injection of anti-vascular endothelial growth factor or cataract extraction). Best corrected visual acuity (BCVA) with and central macular thickness (CMT) using optical coherence tomography (OCT) were measured before each injection in the nAMD group. Aqueous cytokine levels were determined by immunoassay using a multiplex array (Quansys Biosciences, Logan, UT). Levels of ANG2 in the aqueous were significantly higher in nAMD patients than those of the control group (p < 0.0001), so were hepatocyte growth factor (HGF), interleukin-8 (IL-8) and tissue inhibitor of metalloproteinase 1 (TIMP 1), all with p < 0.001. ANG2 correlated with worse BCVA (r = 0.44, p-value = 0.027) and greater CMT (r = 0.66, p-value < 0.0001) on optical coherence tomography (OCT). ANG2 is upregulated in patients with nAMD and correlates with severity of disease at presentation.

Choroidal structures in polypoidal choroidal vasculopathy, neovascular age-related maculopathy, and healthy eyes determined by binarization of swept source optical coherence tomographic images.

PURPOSE: To evaluate quantitatively the choroidal vascularity in polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) patients compared to healthy controls. METHODS: All eyes underwent swept source optical coherence tomography (OCT), and choroidal images were binarized into blood vessels lumen and stroma. The choroidal vascular index (CVI) was defined as the ratio of luminal area (LA) over total choroidal area of the subfoveal region with a width of 1500 µm. RESULTS: The study included 73 patients with neovascular AMD or PCV with mean ± standard deviation (SD) age of 71.8 ± 9.3 years, which was older than the mean age of 65.1 ± 10.8 years of 72 healthy eyes from control group (p < 0.01). The 44 PCV eyes had significantly higher mean SFCT of 214.23 ± 95.21 µm than neovascular AMD eyes (172.74 ± 96.48 µm, p = 0.03) and greater luminal area (0.23 ± 0.09 mm2 vs. 0.19 ± 0.08 mm2, p = 0.05). After adjusting for age, axial length, and gender in multivariate regression analysis, the SFCT of PCV and neovascular AMD eyes were not significantly different from healthy eyes (195.55 ± 93.11 µm), but the CVI of both PCV (64.94 ± 5.43%, p = 0.01) and neovascular AMD (62.54 ± 5.57%, p = <0.01) were significantly lower than control (68.53 ± 5.91%). CONCLUSION: Despite physiological changes of choroidal vasculature due to aging, the choroidal morphology is different in PCV, neovascular AMD and healthy eyes, which has implication on disease pathogenesis.

Classification of Exudative Age-Related Macular Degeneration With Pachyvessels on En Face Swept-Source Optical Coherence Tomography.

Purpose: The purpose of this study was to classify exudative maculopathy by the presence of pachyvessels on en face swept-source optical coherence tomography (SSOCT). Methods: Consecutive patients with signs of exudative maculopathy underwent SSOCT, fluorescein and indocyanine green angiography (ICGA), ultra-widefield fundus color photography, and autofluorescence examinations. Images were analyzed in a masked fashion by two sets of four examiners in different sessions: (1) the presence of pachyvessels in en face OCT and (2) features of exudative maculopathy in conventional imaging modalities. Quantitative data obtained were subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI), which was the ratio of choroidal vessels lumen area to a specified choroidal area from binarized cross-sectional OCT scans. Results: Pachyvessels was observed in 38 (52.1%) of 73 eyes. The pachyvessels group was associated with younger age (69.1 ± 9.4 years, odds ratio [OR] = 0.95, 95% confidence interval [95% CI] = 0.90-0.97, P = 0.04), presence of polypoidal lesions (OR = 3.27, 95% CI = 1.24-8.62, P = 0.01), increased SFCT (OR = 1.08, 95% CI = 1.02-1.14, P < 0.01), and increased CVI (65.4 ± 5.3, OR = 1.12, 95% CI = 1.02-1.23, P = 0.01). In multivariate regression, CVI significantly correlated with pachyvessels (OR = 1.24, 95% CI = 1.03-1.55, P = 0.04). Conclusions: Exudative maculopathy could be classified based on differences in choroidal vasculature morphology. Current results implied that choroidal hemodynamics may be relevant to variable natural history and treatment response in neovascular AMD and polypoidal choroidal vasculopathy.

A Multicenter Study on the Long-term Outcomes of Half-dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate long-term efficacy and prognostic factors of half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR). DESIGN: Retrospective multicenter interventional case series. METHODS: Patients with chronic CSCR undergoing half-dose PDT between 2005 and 2011 were reviewed. Main outcome measures included resolution of serous retinal detachment (SRD) with single PDT, change in best-corrected visual acuities (BCVAs), and recurrence rate of CSCR at 36 months after PDT. Prognostic factors of visual outcome and recurrence of CSCR after PDT were identified with multivariate regression analysis. RESULTS: A total of 136 eyes of 123 patients were followed up for 57.7 ± 16.2 months. At 36 months after PDT, 132 eyes (97.1%) achieved complete resolution of SRD with single PDT and 4 eyes (2.9%) had CSCR recurrence. The mean logMAR BCVA improved from 0.36 ± 0.29 (Snellen equivalent 20/46; range: 0.1-1.2) at baseline to 0.15 ± 0.23 at 36 months (Snellen equivalent 20/28; range: 0.1-1.5; P < .001) and 0.16 ± 0.24 (Snellen equivalent: 20/29; range: 0.1-1.5; P < .001) at final follow-up. Forty-four eyes (32.4%) had ≥3 lines of BCVA gain while 5 eyes (3.7%) had ≥3 lines of BCVA loss at 36 months after PDT. Nine eyes (6.6%) developed CSCR recurrence at final follow-up. Baseline BCVA was significantly associated with the BCVA (P = .009) and the improvement in BCVA (P < .001) at final follow-up. History of bilateral CSCR was significantly associated with CSCR recurrence at final follow-up (P = .036; odds ratio = 15.84, 95% confidence interval = 1.20-208.32). Eight eyes (5.9%) had complications related to PDT. CONCLUSIONS: Chronic CSCR patients treated with half-dose PDT can achieve long-term stable visual acuity and resolution of SRD. Patients with chronic CSCR are recommended to undergo half-dose PDT before they have significant visual deterioration. Patients with bilateral CSCR are more likely to develop CSCR recurrence after half-dose PDT.