Diagnosis and Staging of Pediatric Non-Alcoholic Fatty Liver Disease: Is Classical Ultrasound the Answer?

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.

An Uncommon Aflibercept Side Effect: Full Thickness Macular Hole Formation After Intravitreal Injections in Patients With Pre-existing Vitreomacular Traction.

Aflibercept is an intravitreally injected anti-vascular endothelial growth factor, commonly used in patients with several retinal pathologies, including neovascular age-related macular degeneration. We report a case series of three patients under treatment with an aflibercept regime for neovascular age-related macular degeneration, who were referred to vitreoretinal service between 2015-2016. In all cases, pre-existing vitreomacular traction was detected with an optical coherence tomography scan. All of them developed full-thickness macular hole after aflibercept intravitreal injections. The combined cataract and macular hole surgery was successful, with improvement in visual acuity. We suggest that dynamic alterations of the size of the pigment epithelium detachment resulting from intravitreal injections might intensify the pre-existing pathological adhesion of the vitreous-retinal interface and subsequently cause the formation of a full-thickness macular hole. Therefore, all practitioners treating patients with aflibercept intravitreal injections and pre-existing vitreomacular traction should be aware of the possible macular hole formation.

Morphological Characteristics of Drug-Eluting Biodegradable Polymeric Thin Films Developed on the Surface of Intraocular Lenses by Three Techniques: A Comparative Study.

Background Cataract surgery is a very popular operation that requires a postoperative period of frequent instillation of antibiotic and anti-inflammatory eye drops. Modified drug-eluting intraocular lenses (IOLs) may eliminate the need for eye drops after surgery. Aim The purpose of this study is to compare the morphological characteristics of dexamethasone eluting biodegradable polymeric thin films developed on the surface of commercially available IOLs by three different methods. Method This experimental study was conducted between May and August of 2021 in the Lab for Thin Films - Nanobiomaterials - Nanosystems & Nanometrology (LTFN) of the Aristotle University of Thessaloniki. A mixture of two organic polymers [Poly (D, L-lactide-co-glycolide)(PLGA), lactide: glycolide (75:25) and Polycaprolactone (PCL)] and dexamethasone was prepared and then deposited on the surface of three-piece IOLs by spin coating, by spray coating, and by gravure printing. The modified IOLs were sterilized with the use of ultraviolet (UV) radiation and plasma treatment. Their structural properties were studied with the use of atomic force microscopy (AFM). Results Spin coating and gravure printing produced uniform thin films on the surface of the IOLs which were not damaged during the sterilization process. Spray coating led to the partial coating of the surface of the IOLs; the thin films underwent alterations following plasma treatment. Conclusions Thin films developed by spin coating and gravure printing on IOLs demonstrate the desired morphological characteristics that make them suitable candidates for further research.

Management of acute submacular hemorrhage using intravitreal injection of tissue plasminogen activator and gas: A case series.

The objective of this case series is the evaluation of the efficacy and visual outcomes after displacement of subretinal hemorrhage using intravitreal injection of recombinant tissue plasminogen activator, expansile gas, and in some cases an anti-vascular endothelial growth factor agent. A case series of 28 eyes of 28 patients (16 men and 12 women with age range 67-95 years) suffering from subretinal hemorrhage (duration range 1-15 days) caused by age-related macular degeneration or retinal macroaneurysm is presented. All the patients were treated with intravitreal injection of recombinant tissue plasminogen activator and gas and some of them received an anti-vascular endothelial growth factor agent between January 2013 and December 2016. The outcomes assessed were visual acuity (preoperatively 1 week, and 1 month postoperatively) with respect to duration and dimension of hemorrhage, displacement of hemorrhage, and possible complications of the procedure. Successful displacement of hemorrhage was achieved in 25 patients (89.3%), 18 of 28 patients had significant improvement in visual acuity 1 week after the treatment, and 22 of 28 patients had significant improvement in visual acuity 1 month after the treatment. The mean improvement of all patients with anatomical displacement of the hemorrhage in visual acuity was 0.7 ± 0.5 (LogMAR) in 1 month. Two patients developed vitreous hemorrhage after the procedure and one retinal detachment. Visual outcome a month after therapy displayed week correlation with duration, diameter, and thickness of hemorrhage. The results lead to the conclusion that intravitreal treatment of recombinant tissue plasminogen activator and expansible gas with or without injection of anti-vascular endothelial growth factor agent is effective in improving visual acuity and displacing submacular hemorrhage secondary to age-related macular degeneration and retinal macroaneurysm. The best functional outcomes can be expected in patients regardless of the size and duration of the hemorrhage.

Histological Effects of Intravitreal Injection of Antifungal Agents in New Zealand White Rabbits: An Electron Microscopic and Immunohistochemical Study.

Fungal endophthalmitis is a serious and vision-threatening infection which requires an immediate and effective treatment approach. Our research aims to elucidate the histological effects of the intravitreal injection of the maximum safe dosage of voriconazole and micafungin on retina. Six albino New Zealand White Rabbits were used. In experimental animals, a solution of voriconazole (Group V) or micafungin (Group M) was intravitreally injected in the right eye, while in control animals, balanced salt solution was intravitreally injected in the left eye (Group C). Euthanasia was performed ten days post injection and the retina was removed and prepared for histological examination with a light and electron microscope. Eosin-hematoxylin staining did not reveal any pathological changes in any of the samples examined. The immunohistochemical staining for Tumor Necrosis Factor alpha (TNF-a) marker was detected as negative in all samples, while Interleukin 6 (IL-6) marker was detected as mild only in the group injected with voriconazole. Electron microscopy revealed several ultrastructural alterations in retinal layers in both groups of experimental animals. Histological retinal lesions, revealed with electron microscopy in the present investigation, raises the question of the safe usage of these antifungal agents in the treatment of fungal intraocular infections in the future.

Design, characterisation and drug release study of polymeric, drug-eluting single layer thin films on the surface of intraocular lenses.

To design, develop and study a novel drug delivery system for intraocular applications. The spin coating technique was applied to develop a polymeric, drug-eluting thin film consisting of a blend of organic polymers [poly (D, L lactide coglycolide) lactide: glycolide 75: 25, PLGA and polycaprolactone, PCL] and dexamethasone on the surface of intraocular lenses (IOLs). The initial durability of the IOLs during spinning was assessed. Information about the structural and optical properties of the modified IOLs was extracted using atomic force microscopy, scanning electron microscopy and spectroscopic ellipsometry. A drug release study was conducted for 8 weeks. The IOLs were durable in spinning speeds higher than the ones used to develop thin films. Single-layer thin films were successfully developed on the optics and the haptics of the lenses. The films formed nanopores with encapsulated aggregates of dexamethasone. The spectroscopic ellipsometry showed an acceptable optical transparency of the lenses regardless of the deposition of the drug-eluting films on their surface. The drug release study demonstrated gradual dexamethasone release over the selected period. In conclusion, the novel drug-eluting IOL system exhibited desired properties regarding its transparency and drug release rate. Further research is necessary to assess their suitability as an intraocular drug delivery system.

Ophthalmology Training in Greece as Perceived by Resident Ophthalmologists in the Times of Crisis: A National, Questionnaire-based Survey.

PURPOSE: To assess the level of perceived satisfaction with the current level of ophthalmology training in Greece from the perspective of residents and to identify deficiencies in the training curriculum. METHODS: This is a prospective, cross-sectional questionnaire-based study. An online, semi-structured questionnaire was designed to evaluate ophthalmology residents' extent of satisfaction with the quality of their postgraduate medical training. The survey was divided in two parts: demographics and evaluation of training. Resident ophthalmologists in all teaching hospitals in Greece were contacted and encouraged to complete it. RESULTS: A response rate of 53.8% was achieved. Two out of three participants stated their disappointment with the quality of training they received and deemed the four-year residency training program as insufficient. Surgical training was also viewed as unsatisfactory by the majority of the respondents. An interest in subspecialty training, as well as a significant participation in research activities, was noted. CONCLUSIONS: Both training and overall satisfaction with working conditions must be improved to preserve the appeal of ophthalmology for young academics. A new, structured curriculum, reduction of unnecessary bureaucracy, and improved surgical training rank among the most essential priorities in order to improve postgraduate ophthalmology training.

Ease of Hydrodissection during Phacoemulsification: A Comparison between Patients with and Those without Exfoliation Syndrome.

BACKGROUND: Exfoliation syndrome (XFS), which is associated with increased surgical complications during phacoemulsification, has a relatively high incidence in Greece. Multiannual surgical experience in XFS patients has led to the clinical observation that hydrodissection occurs more easily in XFS patients. OBJECTIVE: To compare the ease of hydrodissection between cataract patients with and those without XFS. METHODS: One hundred and fifteen patients with senile cataract were included in the study. Forty-two of them had XFS. All patients underwent uneventful phacoemulsification by the same surgeon. For hydrodissection, three 1-mL insulin syringes were filled with 0.5 mL balanced salt solution (BSS). Sequentially, each one was quickly and continuously injected underneath the 3, 6, and 9 o'clock positions of the anterior lens capsule. If lens mobilization was achieved with this procedure, hydrodissection was characterized as "easy." RESULTS: The two groups were matched for age, gender, the biomicroscopic type of cataract, and the presence of diabetes mellitus. Glaucoma occurred more often among the XFS patients (p = 0.002). In 39 of the 42 exfoliation patients (92.8%), "easy" hydrodissection was recorded. In the control group, the corresponding number was 47 out of 73 (64.3%). The two groups differed significantly (p = 0.001). CONCLUSIONS: Hydrodissection was more easily performed on the XFS patients than on the controls. This finding could be related to the extensive ultrastructural subepithelial alterations of the anterior lens capsule in XFS, as recently described in electron microscopy studies. We suggest that less BSS can be used for hydrodissection in XFS patients during phacoemulsification.

Design and fabrication of drug-eluting polymeric thin films for applications in ophthalmology.

To study the development, characterisation, and drug release of one- and two-layered thin films based on organic polymers [poly(D,L-lactide-co-glycolide) lactide:glycolide (65:35), poly(D,L-lactide-co-glycolide) lactide:glycolide (75:25), and polycaprolactone] and dexamethasone. To examine their applicability for intraocular lenses (IOLs) and function in intraocular drug delivery systems. Four series of thin films, single and double-layer, were prepared by the spin-coating method on a silicon substrate. The films were studied using atomic force microscopy and spectroscopic ellipsometry. The release rate of dexamethasone was studied for a period of ten weeks. Series A and C demonstrated the formation of large dexamethasone aggregates. The monolayer films of series C and D formed pores, in agreement with previous findings. The spectroscopic ellipsometry study demonstrated that the samples were transparent. The drug release study demonstrated that dexamethasone was released during the first 6 weeks at a desirable rate. The films exhibited properties suitable for use in intraocular drug delivery systems. The single-layer thin films demonstrated a sufficient encapsulation of dexamethasone and appropriate release of the therapeutic substance. Further studies are necessary to investigate the possibility of developing the films directly on the surface of the IOL.

Corneal collagen cross-linking for progressive keratoconus in pediatric patients: a feasibility study.

PURPOSE: To evaluate the outcomes of corneal collagen cross-linking (CXL) in pediatric patients with bilateral progressive keratoconus. METHODS: This retrospective case series included four pediatric patients (eight eyes) with progressive keratoconus aged 14.0±2.2 years (range: 11 to 16 years). All eyes underwent CXL in accordance with the standard Dresden protocol. Pre- and 1-, 12-, 24-, and 36-month postoperative examinations included corneal thickness at the thinnest point (using a topographic system), corneal topographic evaluation (flat and steep meridian keratometry [K1 and K2]), refraction, and visual acuity. RESULTS: All patients completed 36-month follow-up. No intra- or postoperative complications were observed. Stabilization of K1 and K2 was demonstrated in all cases throughout follow-up (from the first postoperative interval), while visual acuity improved in six eyes and remained stable in the remaining two eyes. Manifest refraction remained stable, and corneal thickness decreased at the first postoperative month with gradual return to preoperative values during follow-up. CONCLUSIONS: Preliminary data of four pediatric patients with moderate keratoconus show feasibility of treatment by CXL in these select patients with no intra- or postoperative complications over 3-year follow-up.

Comparison between normal values of 2- and 5-minute Schirmer test without anesthesia.

PURPOSE: To compare the 2- and 5-minute Schirmer test I (test without anesthesia) in healthy individuals so as to exploit the possibility of using the 2-minute instead of the 5-minute test. MATERIAL AND METHOD: 162 healthy (81 males and 81 females) individuals (without dry eye symptoms and free of pathology affecting tear secretion and tear drainage), aged between 20 and 85 years, were recruited in the study (3 age-groups: 20-45, 46-65, and 66-85 years). Schirmer test I (test without topical anesthesia) was performed in both eyes simultaneously. The values of tear secretion were recorded in 2 and 5 minutes and compared in relation to age and gender. The patients were asked to comment on the duration and the discomfort they felt. RESULTS: In 2 minutes, the average tear secretion was 12.71 +/- 2.47 mm (mean +/- SD) for the right eyes and 12.62 +/- 2.09 mm for the left eyes and in 5 minutes, 16.74 +/- 3.59 and 16.831 +/- 3.38 mm, respectively. For confidence interval of 99%, the mean values of tear secretion, in individuals who were expected to have normal secretion, were higher than 10 mm in 2 minutes and higher than 13 mm in 5 minutes (significance level 1% or a = 0.01). Only 5.55% of the eyes presented values <10 mm (7-9.5 mm) in the 2-minute test and values <13 mm (8.5-12.5 mm) in the 5-minute test. There was no significant difference in tear secretion between males and females, between the different age-groups, and between right and left eyes. All the examined individuals expressed their negative comments and considered the test as an unpleasant procedure and consequently preferred the shorter possible duration. CONCLUSION: The 2-minute test is more acceptable by both the examiners and the examined individuals and may be used, in respect to the above results, as an alternative of the 5-minute test. Normal individuals tend to have Schirmer test I values > or = 10 mm in 2 minutes, irrespective of age and gender.