Antioxidant Defense and Pseudoexfoliation Syndrome: An Updated Review.

Oxidative stress (OS) affects the anterior ocular tissues, rendering them susceptible to several eye diseases. On the other hand, protection of the eye from harmful factors is achieved by unique defense mechanisms, including enzymatic and non-enzymatic antioxidants. The imbalance between oxidants and antioxidants could be the cause of pseudoexfoliation syndrome (PEXS), a condition of defective extracellular matrix (ECM) remodeling. A systematic English-language literature review was conducted from May 2022 to June 2022. The main antioxidant enzymes protecting the eye from reactive oxygen species (ROS) are superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which catalyze the reduction of specific types of ROS. Similarly, non-enzymatic antioxidants such as vitamins A, E and C, carotenoids and glutathione (GSH) are involved in removing ROS from the cells. PEXS is a genetic disease, however, environmental and dietary factors also influence its development. Additionally, many OS products disrupting the ECM remodeling process and modifying the antioxidative defense status could lead to PEXS. This review discusses the antioxidative defense of the eye in association with PEXS, and the intricate link between OS and PEXS. Understanding the pathways of PEXS evolution, and developing new methods to reduce OS, are crucial to control and treat this disease. However, further studies are required to elucidate the molecular pathogenesis of PEXS.

Fibroblast Growth Factor-2 (FGF-2) Expression in Pterygia Using Cell Spot Arrays.

Fibroblast growth factor (FGF) is a main regulator of cell differentiation, cell migration and angiogenesis in normal and abnormal conjunctiva epithelia, but specific mechanisms of its aberrant expression are yet to be investigated. In the present study, we investigated FGF-2 protein expression within several pterygia. Using a liquid-based cytology assay, we obtained cell specimens from pterygia and healthy tissues directly from patients. A combination of immunocytochemistry followed by digital image analysis showed significant overexpression of FGF-2 in all the examined pterygia. In 30/60 (50%) cases there were high levels of staining intensity, whereas in the remaining 30/60 (50%) cases there were moderate levels of expression. FGF-2 levels of the control group were significantly lower in comparison with the pterygia group. There was no significant correlation between FGF-2 levels and either sex or location of the pterygium. FGF-2 levels had a significant correlation with morphological characteristics of the pterygia. More specifically, FGF-2 levels were significantly higher in the pterygia with a fleshy morphology. Interestingly, recurrent lesions demonstrated high expression levels. An overexpression of FGF-2 has been observed frequently in pterygia, where it may play a crucial role in determining the lesion's progression. FGF-2 upregulation correlates with the morphology of pterygia and its tendency to recur. Cell spot analysis based on liquid-based cytology is a simple, yet effective, method for detecting a broad spectrum of protein markers and could be useful in analyzing potential pterygia patient samples.

Aqueous Humour Ofloxacin Concentration after Topical Instillation in Patients with Dry Eye Disease.

Background and Objectives: A prospective, randomized clinical trial was conducted to evaluate the concentration of ofloxacin in the aqueous humour (AqH) of patients suffering from dry eye disease (DED) after topical instillation. Materials and Methods: Ninety-one (91) cataract patients scheduled for phacoemulsification were categorized into three groups according to DED severity. Group I (n = 17) was comprised of subjects without DED, patients in group II (n = 37) were evaluated as having non-severe DED, while group III (n = 37) consisted of patients suffering from severe DED. Preoperatively, patients received 4 drops of 0.3% of ofloxacin at 15 min intervals. One hour after the last instillation, aqueous samples were collected intraoperatively. Results: The median AqH concentration of ofloxacin in group I was 199.9 ng/mL (range 92.2−442.8 ng/mL), while in group II it was 530.5 ng/mL (range 283.7−1004.9 ng/mL), and 719.2 ng/mL (range 358.0−1512.4 ng/mL) in Group III, p < 0.001 (Kruskal-Wallis tests). Pairwise tests (two-tailed with Bonferroni corrections) between groups resulted in a p-value of 0.001 when group II was compared to group I and group III was compared to group I, and a p-value of 0.020 when group II was compared to group III. The severity of DED, across groups I, II, and III, and the levels of ofloxacin revealed a strong positive correlation (r = 0.639, p < 0.001). Conclusions: Ofloxacin concentration in the AqH after topical drop instillation may be affected by the degree of ocular surface inflammation in patients suffering from DED.

Emerging roles of oxidative stress in the pathogenesis of pseudoexfoliation syndrome (Review).

Pseudoexfoliation syndrome (PEXS) is a systemic disease caused by defects in the extracellular matrix (ECM) remodelling process leading to the chronic deposition of extracellular, fibrillary, white flaky pseudoexfoliation material (PEXM) throughout the body. Specifically, PEXM deposits on the lens capsule cause open-angle glaucoma, cataracts and blindness in patients with PEXS. Several gene single nucleotide polymorphisms are linked to the development of PEXS in humans, including lysyl oxidase-like 1 gene, clusterin and fibulin-5. The exact reason for the PEXM generation and its resulting pathogenesis is not well understood. However, defective ECM remodelling and oxidative stress (OS) have been hypothesized as significant events leading to the PEXM. Specifically, the link between OS and PEXS has been well studied, although the investigation is still ongoing. The present review explored recent advances in various aspects of PEXS and the involvement of OS in the eye for PEXS development.

Nanotechnology-based formulations to amplify intraocular bioavailability.

Conventional drug delivery formulations, such as eye drops and ointments, are mainly administered by topical instillation. The topical delivery of ophthalmic drugs is a challenging endeavor despite the eye is easily accessible. Unique and complex barriers, serving as protection against extrinsic harmful factors, hamper therapeutic intraocular drug concentrations. Bioavailability for deeper ocular tissues of the anterior segment of the eye is exceptionally low. As the bioavailability of the active substance is the major hurdle to overcome, dosing is increased, so the side effects do. Both provoke patient poor compliance, confining the desired therapeutic outcome. The incidence and severity of adverse reactions amplify evenly in the case of chronic treatments. Current research focuses on the development of innovative delivery strategies to address low ocular bioavailability and provide safe and convenient dosing schemes. The main objective of this review is to explore and present the latest developments in ocular drug delivery formulations for the treatment of the pathology of the anterior segment of the eye. Nanotechnology-based formulations, that is, organic nanoparticles (liposomes, niosomes/discosomes, dendrimers, nanoemulsions, nanosuspensions, nanoparticles/nanospheres) and inorganic nanoparticles, nanoparticle-laden therapeutic contact lenses, in situ gelling systems, and ocular inserts, are summarized and presented accordingly.

Kyrieleis Arteriolitis Associated with Acute Retinal Necrosis due to Herpes Simplex Virus Type 1 Secondary to Herpetic Encephalitis.

We report the case of a 52-year-old woman who presented to the emergency department with acute retinal necrosis in her left eye secondary to herpes simplex virus type 1 encephalitis for which she had been hospitalized four months before. Treatment with intravitreal foscarnet and intravenous acyclovir was promptly commenced followed by the addition of oral prednisolone. PCR analysis of aqueous humor detected HSV type 1 DNA. The condition responded to therapy with partial resolution of intraocular inflammation and improvement of visual acuity, but the presence of Kyrieleis plaques was observed two weeks after the initiation of treatment, when five intravitreal foscarnet injections had been administered. The patient was switched to oral therapy with valacyclovir, and 10 weeks after commencing treatment, the patient's left eye was free of inflammation, having achieved a BCVA of 20/20. Oral steroid treatment was gradually tapered off, and the patient was instructed to remain on prophylactic antiviral therapy. Kyrieleis arteriolitis is an uncommon finding in the context of acute retinal necrosis. As far as we are aware, we report the first case of Kyrieleis arteriolitis in acute retinal necrosis secondary to viral encephalitis and the second one presenting Kyrieleis plaques in acute retinal necrosis caused by herpes simplex virus type 1. Prior reports of cases of Kyrieleis arteriolitis in acute retinal necrosis are also presented.

Effect of Intravitreal Injection of Aflibercept on Cardiovascular Risk Parameters in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: Systemic administration of anti-Vascular Endothelial Growth Factors (anti- VEGFs) has been associated with severe cardiovascular adverse events in oncologic patients. The purpose of this pilot study is to evaluate the short-term effect of a single intravitreal injection of aflibercept on biomarkers related to increased risk of cardiovascular disease. PATIENTS AND METHODS: Forty-seven treatment naïve patients with neovascular age-related macular degeneration in one eye were enrolled in the study. The patients underwent treatment with one intravitreal injection of aflibercept in the affected eye. Laboratory biomarkers of cardiovascular disease were evaluated before the first intravitreal injection of aflibercept and at 7 and 30 days after aflibercept administration. More precisely, we evaluated the levels of homocysteine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and Creactive protein. RESULTS: There was not any statistically significant change in the levels of the evaluated parameters up to one month after the first intravitreal injection of aflibercept. CONCLUSION: According to our study, the administration of a single dose of aflibercept in eyes with neovascular age-related macular degeneration does not seem to affect the evaluated biomarkers that are related to cardiovascular disease.

The Acute Effects of Electronic Cigarette Vaping and Tobacco Cigarette Smoking on Choroidal Thickness in Young, Healthy, Habitual, Dual Smokers.

The present study aims to evaluate and compare the acute effects of tobacco cigarettes (TC) smoking and electronic cigarette (EC) vaping on foveal and choroidal thickness (CT) in young, healthy, dual smokers. Participants underwent four trials: 5 min TC; 5 min EC; 30 min EC; and 60 min nothing (sham trial). Scans before and immediately after each trial were obtained using spectral domain optical coherence tomography with the enhanced depth imaging mode. Changes in central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and CT at fourother points, 500 µm and 1000 µm temporally and nasally to the fovea, were measured. Forty-seven participants (33 male, 14 female; mean age 24.85 ± 1.57 years) were included. They smoked 13.53 ± 5.27 TCs/day for 6 ± 2.3 years and vaped ECs for the past 2.4 ± 1.08 years. We did not observe any statistically significant change in SFCT, CFT, and CT of the other points after any of the fourtrials. The acute changes in CFT and CT after EC vaping or TC smoking did not differ significantly compared to the sham trial. Smoking and vaping does not seem to result in statistically significant acute alterations in foveal and CT in young, dual smokers.

Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration.

PURPOSE: Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. METHODS: Treatment-naïve patients with age-related macular degeneration (n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. RESULTS: The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. CONCLUSION: A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. CLINICALTRIALSGOV ID: NCT03509623.

Brinzolamide-brimonidine fixed combination for the prevention of intraocular pressure elevation after phacoemulsification.

AIM: To evaluate the effectiveness of brinzolamide-brimonidine fixed combination to control the intraocular pressure elevation throughout the first 24 h following uncomplicated phacoemulsification cataract surgery. PATIENTS AND METHODS: A total of 62 patients who underwent phacoemulsification cataract surgery were included in this prospective randomized comparative case series. The brinzolamide-brimonidine fixed combination group (34 eyes) was administered a single dose of brinzolamide-brimonidine fixed combination immediately after phacoemulsification. No treatment was administered in the control group (28 eyes). Intraocular pressure was measured 1 day before surgery (baseline) and at 6, 12 and 24 h postoperatively. RESULTS: The brinzolamide-brimonidine fixed combination group had significantly lower intraocular pressure at 6, 12 and 24 h after phacoemulsification compared to baseline (p < 0.0001 for all comparisons), while in control group, intraocular pressure was significantly higher at 6 and 12 h after surgery compared to baseline (p < 0.001 and p < 0.0001, respectively). In control group, an intraocular pressure elevation ⩾ 5 mm Hg was noted in 32.4% of the eyes at 6 and 12 h and in 5.9% of eyes at 24 h after surgery, while in brinzolamide-brimonidine fixed combination group, only 8.8% of the eyes at 6 h postoperatively had such an intraocular pressure elevation. CONCLUSION: The administration of a single drop of brinzolamide-brimonidine fixed combination effectively prevented intraocular pressure elevations and intraocular pressure spikes during the first 24 h after uneventful phacoemulsification.

Bacteriology and Antimicrobial Susceptibility Patterns of Childhood Acute Bacterial Conjunctivitis in Western Greece.

Acute bacterial conjunctivitis is a common, highly contagious infection in children and is usually treated empirically with broad spectrum topical antibiotics. In the current study we investigated bacteriology and antibiotic susceptibility patterns in childhood acute bacterial conjunctivitis in Western Greece. We conducted a retrospective analysis of presumed acute bacterial conjunctivitis cases in ''Karamandaneio'' Pediatric General Hospital of Patras, Western Greece, between February 1, 2013 and January 31, 2018. Specimens from the lower conjunctiva fornix were isolated from 191 cases and outcomes were analyzed to identify the pathogenic bacteria of acute bacterial conjunctivitis and their corresponding antibiotic susceptibility patterns. Patients were divided into 3 groups; Group A included neonates under 28 days of life, Group B children from 1 month to 2 years and Group C from 2 years to 14 years. Results revealed that Staphylococcus spp., Haemophilus spp. and Streptococcus spp. were the most prevalent pathogens. No significant differences in isolated pathogens were found between the age groups. Antibiotic resistance rates were higher against ampicillin, ceftriaxone, ceftazidime and sulfamethoxazole. Resistance rates to Ciprofloxacin were low while none of the evaluated isolates were resistant to vancomycin. We concluded that predominant pathogens of childhood acute bacterial conjunctivitis in Western Greece were Staphylococcus spp., Haemophilus spp. and Streptococcus spp. Continuous surveillance, focused in distinct geographic areas, is encouraged to prepare more precise protocols of empirical treatment.

Analgesic Effect of a Single Drop of Nepafenac 0.3% on Pain Associated with Intravitreal Injections: A Randomized Clinical Trial.

PURPOSE: To evaluate the analgesic effect of nepafenac 0.3% in patients undergoing intravitreal injections (IVI) of antivascular endothelial growth factors. METHODS: This is a single-center, prospective, randomized, blinded, triple-arm, placebo-controlled interventional study. Patients were randomized into 3 Groups. Group 1 (n = 33) received nepafenac 0.1%, Group 2 (n = 32) received nepafenac 0.3%, and Group 3 (n = 31) received placebo 40 min before IVI. Using the short form of the McGill Pain Questionnaire (SF-MPQ), pain intensity was assessed with the visual analog scale (VAS), the Main Component of the SF-MPQ, and the present pain intensity (PPI) scores immediately and 6 h postinjection. RESULTS: Immediately after IVI, the VAS pain score was statistically significantly lower in patients treated with nepafenac 0.1% and 0.3%, compared with placebo (P < 0.001 and P = 0.001, respectively). The PPI scores were statistically significantly lower when nepafenac 0.1% or 0.3% was instilled compared with placebo (P = 0.01 and P < 0.0001, respectively). The Main Component of the SF-MPQ scores were statistically significantly lower after nepafenac 0.1% and 0.3% administration compared with placebo (P = 0.001 and P < 0.001, respectively). Six hours post-IVI the nepafenac 0.3% demonstrated statistically significantly higher analgesic effect compared with nepafenac 0.1% and placebo as this was indicated by the VAS pain score (P = 0.013 and P < 0.00001, respectively) and by the PPI score (P = 0.01 and P < 0.00001, respectively). CONCLUSIONS: A single instillation of nepafenac 0.1% or 0.3% before IVI could effectively alleviate the IVI-related pain. The 0.3% formula exerts its analgesic effect more intensively at 6 h after the IVI.

Dexamethasone implant for immunogammopathy maculopathy associated with IgA multiple myeloma.

BACKGROUND: We describe a case where hyperviscosity retinopathy and immunogammopathy maculopathy were the presenting features of IgA multiple myeloma and report the response of maculopathy to intravitreal injection of dexamethasone implants. CASE PRESENTATION: A 56-year-old man presented at the Department of Ophthalmology with the chief complain of reduced vision for the past 10 days in both eyes. Ophthalmic examination revealed central retinal vein occlusion resembling signs with severe macular edema in both eyes with prominent serous macular detachment. After comprehensive evaluation, an IgA type kappa multiple myeloma was diagnosed complicated with hyperviscosity-associated retinopathy and immunogammopathy maculopathy. Patient was treated with multiple sessions of plasmapheresis, systemic chemotherapy, and finally intravitreal implants of dexamethasone with complete restoration of macular edema and serous macular detachment in both eyes. The visual function and the hyperviscosity-associated retinopathy were partially restored. CONCLUSION: Ocular manifestation might be the only presenting sign of a life-threatening disease such as IgA multiple myeloma. A high level of suspicion is required to diagnose and treat such cases promptly and effectively.

Micropulse laser trabeculoplasty on pseuodexfoliation glaucoma patients under topical prostaglandin analogue monotherapy: 1-year results.

PURPOSE: To evaluate the effectiveness of a single session of micropulse laser trabeculoplasty (MLT) to lower intraocular pressure (IOP) in patients with pseudoexfoliation glaucoma (PEXG). METHODS: In this single-center, one-arm, prospective study patients with PEXG under prostaglandine analogue monotherapy with inadequate IOP control were treated with 360° 532-nm MLT. Patients were evaluated at 1 day, 1 month, 3 months, 6 months, and 12 months post-MLT while they were treated with the same drug regimen as pre-MLT. Mean IOP reduction and percentage of IOP change during the follow-up were calculated. Cases that required any further intervention, like additional hypotensive medication, laser or surgical therapy, throughout the study period were considered failures and removed from the study. RESULTS: Twenty-seven eyes (27 patients, 17 male) were included in the study. The age of the patients was 72.37 ± 6.29 years and the baseline IOP was 20.41 ± 1.87 mmHg. Treatment with MLT resulted in significantly lower IOP at 1, 3, 6, and 12 months after MLT compared to baseline (p < 0.0001 for all comparisons). By the end of the study, 52.17% of the PEXG eyes demonstrated a ≥ 20% IOP reduction compared to baseline. Four eyes (14.81%) did not respond to MLT (three eyes at 3 months and one eye at 6 months after trabeculoplasty) and were considered failures since they required additional intervention. CONCLUSIONS: Micropulse laser trabeculoplasty appears to be an effective method to lower IOP in patients with PEXG up to 12 month of follow-up period. TRIAL REGISTRATION: The study is registered on www.ClinicalTrials.gov with registration number NCT03483402.