Chronic liver disease and oxidative stress - a narrative review.

Introduction: Oxidative stress underlies the pathophysiology of various etiologies of chronic liver disease and contributes to the development of hepatocarcinogenesis.Areas covered: This review focuses on the impact of oxidative stress in various etiologies of chronic liver disease such as alcoholic liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. The efficacy of antioxidants in laboratory, animal, and clinical studies in chronic liver disease is also reviewed.Expert opinion: Currently, there are limited targeted pharmacotherapeutics for NASH and no pharmacotherapeutics for ALD and antioxidant supplementation may be useful in these conditions to improve liver function and reverse fibrosis. Antioxidants may also be used in patients with HBV or HCV infection to supplement antiviral therapies. Specific genotypes of antioxidant and prooxidant genes render patients more susceptible to liver cirrhosis and hepatocellular carcinoma while other individual characteristics like age, genotype, and metabolomic profiling can influence the efficacy of antioxidants on CLD. More research needs to be done to establish the safety, efficacy, and dosage of antioxidants and to establish the ideal patient profile that will benefit the most from antioxidant treatment.

Orbital Implants in Orbital Fracture Reconstruction: A Ten-Year Series.

STUDY DESIGN: Retrospective comparative interventional series of all patients who had undergone orbital fracture repair by 2 senior orbital surgeons in a single tertiary trauma center from January 2005 to December 2014. OBJECTIVE: To compare the outcomes of different implants used for various types of orbital fractures. METHODS: Patients were evaluated by age, gender, etiology of fracture, clinical findings, type of fractures, and implant used. Main outcome measures included restoration of premorbid state without morbidity and complications including enophthalmos, diplopia, infraorbital hypoesthesia, and ocular motility restriction 1 year after fracture repair. Implant-related complications were collected for analysis. RESULTS: There were a total of 274 patients with 307 orbits reconstructed. Thirty-three (12.0%) patients sustained bilateral injuries; 58.0% (n = 178) of orbits had simple fractures (isolated orbital floor, medial wall, or combined floor and medial wall). The distribution of implants used were bioresorbable (n = 117, 38.1%) and prefabricated titanium plates (n = 98, 31.9%) depending upon the nature of fracture. Bioresorbables, titanium plate, and porous polyethylene were used significantly more than titanium mesh for simple fractures, and prefabricated anatomic titanium implants were used significantly more than the other implants for complex fractures. There was a statistically significant improvement in diplopia, enophthalmos, ocular motility, and infraorbital hypoesthesia (p-value < 0.001) 1 year following orbital fracture reconstruction. CONCLUSIONS: When used appropriately, diverse alloplastic materials used in orbital fracture repair tailored to the indication aid orbital reconstruction outcomes with each material having its own unique characteristics.

Visual field progression 8 years after trabeculectomy in Asian eyes: results from The Singapore 5-Fluorouracil Study.

BACKGROUND/AIMS: This work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes. METHODS: This was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints). RESULTS: 127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and ≥8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=-0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=-0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures. CONCLUSION: In post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression.

Choroidal Vascularity Index Using Swept-Source and Spectral-Domain Optical Coherence Tomography: A Comparative Study.

BACKGROUND AND OBJECTIVE: Choroidal vascularity index (CVI) is a noninvasive tool to assess choroidal structure. The objective of the current study was to compare the CVI measurements on swept-source optical coherence tomography (SS-OCT) and spectral-domain OCT (SD-OCT) scans using the same image binarization protocol. PATIENTS AND METHODS: This prospective study was conducted from July 2016 through January 2017 and involved 54 healthy volunteers at a tertiary referral eye care institute in Southern India. Choroidal scans were obtained using both SS- and SD-OCT machines. An automated binarization algorithm was used to compute CVI. RESULTS: The mean CVI with SS-OCT scans was 53.88% ± 12.54% (range: 20.46% to 73.93%), whereas the mean CVI with SD-OCT scans was 51.11% ± 7.97% (range: 29.90% to 67.72%)(P < .001). The unadjusted (95% confidence interval [CI], 0.554-0.851) and adjusted (95% CI, 0.607-0.871) intraclass correlation (ICC) estimates were quite similar and indicate moderate-to-good reliability of measurements by two machines. The interval estimate for a conversion factor between SD-OCT and SS-OCT can be calculated as follows: SD = [0.383*SS+19.467, 0.586*SS+30.661]. CONCLUSION: CVI is a noninvasive, robust, and reliable measurement of choroidal vascularity and CVI measurements obtained using both SS-OCT and SD-OCT concur with each other. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e26-e32.].

Analysis of 130 Cases of Sympathetic Ophthalmia - A Retrospective Multicenter Case Series.

Objective: To analyze the demographic profile, treatment, and visual outcome of the patients with sympathetic ophthalmia (SO) in a multicenter collaborative retrospective cohort study.Methods: Medical records of the patients with SO from UK, Singapore, India were reviewed for history of ocular trauma or surgery and subsequent development of uveitis consistent with SO, presenting symptoms, treatment, and visual outcomes.Results: A total of 130 patients were diagnosed with SO during the study period. Eighty-one (62.3%) patients were men. The mean age was 48.4 ± 15.5 years. The most common presenting symptom was blurring of vision (89.2%), followed by pain (29.2%) and floaters (23.8%). Ninety-two (70.7%) required additional immunosuppressive therapy. Thirty-six (27.9%) patients underwent enucleation of the inciting eye.Conclusions: SO is a potentially sight-threatening disease with high rates of visual loss. It warrants prompt evaluation and treatment. With the advances and availability in immunotherapy, the visual prognosis is relatively good.

Permanent Versus Bioresorbable Implants in Orbital Floor Blowout Fractures.

PURPOSE: To compare the outcomes of bioresorbable and permanent implants in the reconstruction of isolated orbital floor blowout fractures. METHODS: Retrospective series of all patients who had orbital floor fracture repair in a single tertiary trauma center from January 2005 to December 2014. The authors reviewed the case notes and CT scans of patients with orbital floor fracture repair with either bioresorbable or permanent implants. Main outcome measures were enophthalmos, diplopia, and ocular motility restriction 1.5 years after fracture repair. Implant-related complications were collected for analysis. RESULTS: There were a total of 88 patients in our study. Bioresorbable implants were used in 48 patients (54.5%) while 40 patients had permanent implants (45.5%). The authors analyzed the implants used in various sizes of orbital fractures: small (<13.3 mm), medium (13.3-20 mm), and large (>20 mm). One and a half years after fracture repair, both groups had comparable clinical outcomes (n = 2 and n = 0 for diplopia for permanent and bioresorbable implant groups, respectively, n = 0 for enophthalmos for both groups and n = 1 for ocular motility limitation for both groups) overall and across all fracture sizes. CONCLUSION: Bioresorbable implants degrade after fracture healing through hydrolysis and promote the gradual transfer of functional forces to healing bone during its disintegration. The clinical outcomes of diplopia, enophthalmos, and ocular motility restriction associated with the use of resorbable implants are comparable to that of permanent implants for all fracture sizes. Their study shows that bioresorbable and permanent implants are equally safe and effective for the treatment of patients with isolated orbital floor blowout fractures.

Dry eye disease and oxidative stress.

Dry eye, an age-related condition, is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability. Environmental factors are also often implicated in dry eye including exposure to pollutants, ultraviolet (UV) radiation and ozone as well as the chronic use of preserved eyedrops such as in the treatment of glaucoma. These factors increase oxidative stress and ocular surface inflammation. Here, we reviewed the cellular, animal and clinical studies that point to the role of oxidative stress in dry eye disease. The biomarkers used to indicate oxidative damage in ocular surface tissues include 8-hydroxy-2 deoxyguanosine (8-OHdG), 4-hydroxynonenal (HNE) and malondialdehyde (MDD). Antioxidative defences in the ocular surface occur in the form of tear proteins such as lactoferrin and S100A proteins, and enzymes such as superoxide dismutase (SOD), peroxidase, catalase and mitochondrial oxidative enzymes. An imbalance between the level of reactive oxygen species (ROS) and the action of protective enzymes will lead to oxidative damage, and possibly inflammation. A small number of interventional studies suggest that oxidative stress may be directly targeted in topical therapy of dry eye treatment. For example, in vitro studies suggest that L-carnitine and pterostilbene, a blueberry component may reduce oxidative stress, and in animal studies, alpha-lipoic acid (ALP) and selenoprotein P may be helpful. Examples of treatments used in clinical trials include vitamin B12 eyedrops and iodide iontophoresis. With recent emphasis on ageing medicine and preventive holistic health, as well as the role of environmental science, research on oxidative stress in the ocular surface is likely to have increasing impact in the coming years.

Choroidal Remodeling in Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy: A 12-month Prospective Study.

Choroid thinning occurs in age-related macular degeneration (AMD). However, it remains unclear whether the reduction is due to reduction in choroidal vessels or shrinkage of choroidal stroma, or both. The purpose of this study was to evaluate the changes of the choroidal vascular and stromal area in 118 patients with typical AMD (t-AMD) and polypoidal choroidal vasculopathy (PCV) over a 12-month period. We used spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode to measure the subfoveal choroidal thickness (CT), central retinal thickness (CRT) and choroidal vascularity index (CVI - ratio of luminal area to total choroidal area). At baseline, PCV eyes had higher CRT (471.6 µm vs 439.1 µm, p = 0.02), but comparable subfoveal CT and CVI, compared to t-AMD. Eyes with high CVI at baseline showed marked reduction in stromal area compared with eyes with average or low CVI. Over 12 months, CRT and subfoveal CT significantly decreased (p < 0.001) in both subtypes. Eyes with high baseline CVI showed significant CVI reduction from baseline to month 12 (p < 0.001), whereas eyes with average to low baseline CVI showed increase in CVI. These differences in choroidal vascularity may reflect different predominant pathogenic processes and remodeling in AMD eyes with varying spectrum.

Systematic analysis of ocular trauma by a new proposed ocular trauma classification.

PURPOSE: The current classification of ocular trauma does not incorporate adnexal trauma, injuries that are attributable to a nonmechanical cause and destructive globe injuries. This study proposes a new classification system of ocular trauma which is broader-based to allow for the classification of a wider range of ocular injuries not covered by the current classification. METHODS: A clinic-based cross-sectional study to validate the proposed classification. We analyzed 535 cases of ocular injury from January 1, 2012 to February 28, 2012 over a 4-year period in an eye hospital in central India using our proposed classification system and compared it with conventional classification. RESULTS: The new classification system allowed for classification of all 535 cases of ocular injury. The conventional classification was only able to classify 364 of the 535 trauma cases. Injuries involving the adnexa, nonmechanical injuries and destructive globe injuries could not be classified by the conventional classification, thus missing about 33% of cases. CONCLUSIONS: Our classification system shows an improvement over existing ocular trauma classification as it allows for the classification of all type of ocular injuries and will allow for better and specific prognostication. This system has the potential to aid communication between physicians and result in better patient care. It can also provide a more authentic, wide spectrum of ocular injuries in correlation with etiology. By including adnexal injuries and nonmechanical injuries, we have been able to classify all 535 cases of trauma. Otherwise, about 30% of cases would have been excluded from the study.