Risk factors for diabetic retinopathy, diabetic macular edema, and sight-threatening diabetic retinopathy.

OBJECTIVE: To identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program. RESEARCH DESIGN AND METHODS: Diabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. RESULTS: Out of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. CONCLUSIONS: Similar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.

Comparing the Rise in Glucose Concentration in Blood, Aqueous and Interstitial Fluid During a Glucose Tolerance Test.

Purpose: The purpose of the study was to determine if aqueous glucose levels rise in a comparable time frame to interstitial fluid and could therefore be suitable for a continuous glucose monitoring (CGM) site. Methods: An intravenous glucose tolerance test was performed on five New Zealand white rabbits. Aqueous humor from the posterior and anterior chamber of the eye and venous blood were sampled for glucose concentration measurement. Glucose concentrations in the interstitial fluids were monitored using a CGM system. A compartment model was created to map the glucose response curves in each compartment. The delay in rising glucose concentrations between blood and interstitial fluid and aqueous humor in the posterior chamber and anterior chamber of the eye were analyzed. Results: The results showed a statistically similar time lag and rate of change in glucose concentrations between blood and interstitial fluids or aqueous humor in either the posterior or anterior chamber. Conclusions: The results of this study add further support to the aqueous humor being used as an alternative CGM site. Translational Relevance: The study provides the basis for developing an intraocular continuous glucose sensor that can overcome limitations of current CGM systems.

Optical Coherence Tomography Angiography Compared with Multimodal Imaging for Diagnosing Neovascular Central Serous Chorioretinopathy.

PURPOSE: To assess the diagnostic accuracy of optical coherence tomography angiography (OCTA) compared with multimodal imaging for choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC) eyes and to determine the features that predicted CNV. DESIGN: Prospective cross-sectional study. METHODS: Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV. RESULTS: CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean area under the receiver operating characteristic curve (AUC) was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P < 0.001, P < 0.001 and P = 0.005, respectively). CONCLUSIONS: There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.

Clinical features and treatment outcomes of endogenous Klebsiella endophthalmitis: a 12-year review.

AIM: To identify the clinical features and treatment outcomes of endogenous Klebsiella pneumoniae endophthalmitis and investigate prognostic factors of poor visual outcome. METHODS: The clinical records of all patients diagnosed with endogenous Klebsiella endophthalmitis between January 2007 to December 2018 in Prince of Wales Hospital, Hong Kong, China were retrospectively reviewed. Thorough ophthalmological examination findings were recorded in the case note, including visual acuity testing, slit-lamp examination, indirect ophthalmoscopy and B-scan ultrasonography if media opacity precluded fundus viewing. RESULTS: A total of 18 eyes in 14 patients were identified. Bilateral involvement was noted in 4 patients (28.6%). Hepatobiliary sepsis was the source in 9 patients (64.3%). Culture of intraocular fluid was positive in 5 out of 18 eyes (27.8%). Mortality was noted in 2 patients (14.3%). Mean final visual acuity was 20/1500. Six out of 16 eyes had total loss of sight (37.5%) and 3 eyes required evisceration (18.8%). Multivariate linear regression revealed poor presenting visual acuity (P=0.031) and lack of fundus view due to vitritis (P=0.02) as prognostic factors of poor visual outcome. CONCLUSION: Visual outcome of endogenous Klebsiella endophthalmitis is poor. Poor presenting visual acuity and lack of fundus view predict poor visual outcome. High index of suspicion for endophthalmitis is important in Klebsiella sepsis patients with complaints of ocular symptoms. Ophthalmological screening is recommended in non-communicable patients with Klebsiella sepsis.

Evaluation of Electrical Performance and Properties of Electroretinography Electrodes.

Purpose: The aim of this study was to evaluate and compare the electrical performance and properties of commercially available electroretinography (ERG) electrodes. Methods: A passive ionic model was used to measure impedance, noise, and potential drift in 10 types of ocular surface and skin ERG electrodes. Results: The impedance for silver-based ocular electrodes are generally lower (range, 65.35-343.3 Ω) with smaller phase angles (range, -6.41° to -33.91°) than gold-based electrodes (impedance ranged from 285.95 Ω to 2.913 kΩ, and phase angle ranged from -59.65° to -70.01°). Silver-based ocular electrodes have less noise (median line noise of 6.48 x 104nV2/Hz) than gold-based electrodes (median line noise of 2.26 x 105nV2/Hz). Although silver-based electrodes usually achieve a drift rate less than 5 µV/s within 15 minutes, gold-base ocular electrode cannot achieve a stable potential. The exception is the RETeval strip type of silver electrode, which had an unusual drift at 20 minutes. The noise spectral density showed no change over time indicating that noise was not dependent on the stabilization of the electrode. Conclusions: From the range of electrodes tested, lower impedance, lower capacitance, and lower noise was observed in silver-based electrodes. Stabilization of an electrode is effective against drift of the electrode potential difference but not the noise. Translational Relevance: Application of electrodes with optimized materials improve the quality of clinical electrophysiology signals and efficiency of the recording.

Improving the quality of electroretinogram recordings using active electrodes.

The aim of this study was to compare the quality of electroretinogram (ERG) recordings using a custom built active electrode with attached amplifier versus a standard (passive) ERG electrode. Scotopic and photopic ERG responses were recorded from five adult albino rabbits using a custom built active electrode on one eye and a passive electrode on the other. For the active electrode, the ERG-jet electrode (Universo S.A., La Chaux-De-Fonds, Switzerland) was used as the transducer with the cable cut short and soldered directly to the input of a customized amplifier. The passive electrode was a standard ERG jet electrode. The signal to noise ratio and reproducibility of ERGs were compared. The noise was significantly lower in the active electrode compared to the passive electrode (p = 0.009) resulting in signals being recorded at lower stimulation strengths with the active electrode. The scotopic a-wave was significantly larger in the active electrode at all supra-threshold stimulation intensities (p < 0.05) and the scotopic b-wave amplitudes were also higher in the active electrode at all supra-threshold stimulation intensities but was only statistically significant between -3.25 and -1 log cd.s.m-2 (p < 0.05). The photopic a- and b-wave amplitudes were also higher in the active electrode and statistically significant between -0.75 and 0.48 log cd.s.m-2 for the a-wave and -1.25 to -1 log cd.s.m-2 for the b-wave (p < 0.05). The intra-observer repeatability, inter-sessions reproducibility and reliability of the signals were better in the active electrode as evidenced by lower coefficient of variation (CV) and coefficient of repeatability (CR) with high intra-class correlation coefficient (ICC) of the a- and b-wave parameters of the active electrode. These findings suggest that the custom built active ERG electrode produces less noise than the passive electrode, allowing responses to be recorded at lower stimulation strengths. It produces greater signal amplitudes and improved reproducibility and is therefore a better device for investigating retinal function.

Bilateral acute retinal necrosis after bilateral cataract surgery in an immunocompromised patient: a case report.

PURPOSE: To report a case of bilateral varicella zoster virus (VZV)-associated acute retinal necrosis (ARN) occurring after both eyes sequential cataract surgery in an elderly immunocompromised patient. METHODS: Medical records and investigation results of the patient were reviewed. RESULTS: Patient experienced floaters and blurring of vision in both eyes 4 weeks after her second uncomplicated cataract surgery. Clinical signs of granulomatous keratic precipitates, prominent vitritis, retinitis and vascular thrombosis were noted in both eyes. Aqueous samples from both eyes were positive for VZV. Disease was treated with intravitreal foscarnet bilaterally and 10 days of systemic intravenous acyclovir (10 mg/kg) followed by oral valaciclovir 1 g three times daily. Final visual acuity at 4 months after initial presentation was 20/60 in both eyes with no retinal detachment noted. CONCLUSIONS: Cataract surgery may have been the trigger for bilateral VZV-associated ARN. Immunocompromised patients can develop ARN and require close observation after cataract surgery. This is, to our knowledge, the first report of bilateral ARN following routine cataract surgery.

Disruption of retinal pigment epithelial cell properties under the exposure of cotinine.

Cigarette smoking is a major risk factor for age-related macular degeneration (AMD), in which progressive retinal pigment epithelial (RPE) cell degeneration is a major pathological change. Nicotine is a major biologically active component in cigarette smoke. It is continuously catabolized into cotinine, which has longer half-life and higher concentration in tissue cells and fluids. Here we hypothesized that continuous exposure of cotinine has more potent effects on human RPE cell properties than nicotine. Human RPE cell line (ARPE-19) was treated continuously with 1-2 µM of nicotine and/or cotinine for 7 days. RPE cells treated with 2 µM cotinine and nicotine-cotinine mixture has lower MTT signals without significant changes in cell apoptosis or integrity. Moreover, RPE cell migration was retarded under cotinine treatments, but not nicotine. Both nicotine and cotinine treatments attenuated the phagocytotic activity of RPE cells. In addition, cotinine and nicotine-cotinine mixture suppressed VEGF and IL-8 expression and upregulated TIMP-2 expression. Expressions of autophagy genes were upregulated by the cotinine treatment, whereas expressions of epithelial-to-mesenchymal transition markers were downregulated. In conclusion, our study, for the first time, demonstrated that cotinine, rather than nicotine, affects the properties of RPE cells in vitro, which could explain the smoking-induced RPE pathology.

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.

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction.

Age-related macular degeneration (AMD), characterized by progressive degeneration of retinal pigment epithelium (RPE), is the major cause of irreversible blindness and visual impairment in elderly population. We previously established a RPE degeneration model using an acute high dose sodium iodate to induce oxidative stress. Here we report findings on a prolonged treatment of low doses of sodium iodate on human RPE cells (ARPE-19). RPE cells were treated continuously with low doses (2-10 mM) of sodium iodate for 5 days. Low doses (2-5 mM) of sodium iodate did not reduce RPE cell viability, which is contrasting to cell apoptosis in 10 mM treatment. These low doses are sufficient to retard RPE cell migration and reduced expression of cell junction protein ZO-1. Phagocytotic activity of RPE cells was attenuated by sodium iodate dose-dependently. Sodium iodate also increased expression of FGF-2, but suppressed expression of IL-8, PDGF, TIMP-2 and VEGF. Furthermore, HTRA1 and epithelial-to-mesenchymal transition marker proteins were downregulated, whereas PERK and LC3B-II proteins were upregulated after sodium iodate treatment. These results suggested that prolonged exposure to non-lethal doses of oxidative stress induces RPE cell dysfunctions that resemble conditions in AMD. This model can be used for future drug/treatment investigation on AMD.