Role of actin-binding proteins in cataract formation.

INTRODUCTION: Actin has been implicated in lens opacification; however, the specific actin-related pathways involved in cataracts remain unelucidated. In this study, actin-related proteome changes and signaling pathways involved in the development of cataracts were evaluated. METHODS: The anterior capsule and phacoemulsification (phaco) cassette contents were collected during cataract surgery from 11 patients with diabetic cataract (DC), 12 patients with age-related cataract (ARC), and seven patients with post-vitrectomy cataract (PVC). Untargeted, global identification and quantification of proteins was performed through liquid chromatography-mass spectrometry with the data-independent acquisition (DIA). RESULTS: In phaco cassette samples, proteins with significantly lower expression in ARC than in DC and PVC were involved in various pathways, including actin binding, actin cytoskeleton reorganization, actin filament capping, cortical actin cytoskeleton organization, and small GTPase-mediated signal transduction pathways. In anterior capsules, proteins with significantly lower expression in ARC than in DC and PVC were involved in actin binding and actin cytoskeleton reorganization pathways. CONCLUSION: Actin cytoskeleton and actin-binding proteins are involved in lens fiber elongation and differentiation. Rho GTPases contribute to actin cytoskeletal reorganization, and their inactivation is linked to abnormal lens fiber migration. These findings link actin binding to lens fiber integrity, lens opacification, and cataracts.

Lens Cytoskeleton: An Update on the Etiopathogenesis of Human Cataracts.

A cataract is a loss of the transparency of a normal crystalline lens. Multiple factors, including age as the major risk factor for cataracts, can disturb the transparency of the crystalline lens due to cumulative damage from environmental insults to proteins, particularly crystallins. Lens proteins do not turnover, and crystallins undergo extensive post-translational modifications (PTMs) with age in order to interact with each other and maintain their soluble basis for lens transparency. These PTMs include truncation, oxidation, deamidation, acetylation, phosphorylation, and glycosylation. Cataract formation, apart from protein PTMs, involves protein crosslinking, protein insolubilization, and aggregation. Oxidation is a key feature in age-related cataract formation. Due to the role of genetic and environmental factors, as well as its variable clinical presentation, we consider cataracts to be a multifactorial disease. The preliminary results of our study indicate that proteins implicated in the pathway of a structural constituent of the eye lens (BFSP1, BFSP2, CRYAA, CRYAB, CRYBA, CRYBB, CRYGC, CRYGD, CRYGS, KRTs, and VIM), together with AQP1 and AQP5, may also be involved in lens aging.

Macular and Optic Disc Perfusion Changes After Silicone Oil Removal Using Optical Coherence Tomography Angiography: A Prospective Study.

AIM: The aim of this study was to prospectively evaluate the changes in macular and optic disc microvascular structures in patients who underwent silicone oil (SO) removal. MATERIALS AND METHODS: A total of 28 patients scheduled for unilateral SO removal were included in the study. Their fellow eyes served as controls. Optical coherence tomography angiography (OCTA) of the retina (6.0 mm) and disc (4.5 mm) was performed one day before SO removal, and then at 1 week and 1, 3, 6, and 12 months postoperatively. All analyses were conducted using the R programming language, with a p-value <0.05 considered statistically significant. RESULTS: After silicone oil removal, statistically significant changes were observed in the flow in the outer retina and radial peripapillary capillary (RPC) density for small and all vessels inside the disc. Statistically significant differences between the intervention and control groups were noted in vessel density in both the superficial and deep capillary plexuses and RPC density for small and all vessels. CONCLUSION: Changes in macular vessel density and radial peripapillary capillary density were observed after SO removal. The latter changes appear to improve after the first postoperative month and continue until the first postoperative year. Notably, these changes were significant between the first postoperative week and 6 and 12 postoperative months (p = 0.0263 and p = 0.021, respectively). Best corrected visual acuity (BCVA) is likely associated with these parameters, indicating that improvement may be observed even one year following SO removal.

Corneal tomography changes following major (6 mm) medial rectus muscle recession: a prospective cohort study using Pentacam®.

INTRODUCTION: The aim of this study is to evaluate changes in corneal astigmatism, axial anterior corneal curvature, as well as changes in the anterior chamber depth and central corneal thickness, 2 months following the unilateral recession of medial rectus muscle in children. METHODS: Thirty-three children with esotropia were prospectively evaluated following unilateral medial rectus muscle recession, using Pentacam®. Comparisons were made between the operated and fellow unoperated eyes, pre, and postoperatively. The assessment was made for changes in the radius of axial curvature on major meridians at 3 and 3.5 mm from the optical corneal center in the mid-peripheral zone. Astigmatism changes of the anterior and posterior corneal surface were calculated using vector analysis software (astigMATIC®). ANOVA model was used to examine the interaction between age or central corneal thickness and postoperative changes in anterior and posterior surface corneal astigmatism. RESULTS: In the intervention group, changes in anterior and posterior corneal surface astigmatism were statistically significant, with a mean increase of 0.59Dx92 and 0.08Dx91, respectively. In the mid-peripheral corneal zone, there is an increase in the radius of anterior corneal axial curvature more evident nasally 3.5 mm from the corneal center on the horizontal meridian, with corresponding decrease superiorly and inferiorly at 3 and 3.5 mm from the corneal center on the vertical meridian. DISCUSSION: The changes in total astigmatism of the operated eyes are mainly attributed to the anterior corneal surface. These changes are associated with flattening in the 180 meridian of the cornea, leading to a shift to "with-the-rule" astigmatism.

Foveal Hypoplasia in a Child With Tyrosinase-Positive Albinism.

The purpose of this article is to report a case of bilateral foveal hypoplasia in an eight-year-old girl who presented to the ophthalmology department due to poor vision in both eyes. Clinical examination revealed bilateral nystagmus, decreased vision, as well as iris transillumination. Dilated fundus examination indicated the absence of light reflex around the foveal area and optical coherence tomography (OCT) imaging exhibited the absence of the fovea centralis depression. These findings, in addition to the patient's light-colored hair and skin complexion, raised suspicion for albinism. The patient was referred for genetic testing and the results confirmed the diagnosis of tyrosinase-positive oculocutaneous albinism (OCA2).

Evaluation of Macular Thickness Changes Following Large Horizontal Rectus Muscle Recession: A Prospective Cohort Study.

Aim The aim of the study was to evaluate the long-term effect of large horizontal rectus muscle recession on macula thickness using spectral domain optical coherence tomography (SD-OCT). Material and methods Forty-two children were included in the study. The intervention groups were the medial rectus (MR) group (=20 eyes ) and the lateral rectus (LR) group (=22 eyes), including the eyes that underwent large medial and lateral rectus muscle recession, respectively. The control group included the fellow 42 unoperated eyes of the same children. Each eye was scanned using Topcon Maestro2 OCT-Angiography (OCTA; Topcon, Tokyo, Japan) preoperatively and then two months following surgery. A paired t-test was used to compare the mean difference in macular thickness between the intervention and control groups using the statistical program R (R Foundation for Statistical Computing, Vienna, Austria). Results The mean change in central, parafoveal, and perifoveal macular thickness of the intervention group was not statistically significant. Conclusion The long-term changes in macular thickness, as evaluated using SD-OCT both for the central and peripheral regions of the fovea, following large horizontal rectus muscle recession surgery, are not statistically significant.

Acute Macular Neuroretinopathy Associated With COVID-19 Infection: Is Double Heterozygous Methylenetetrahydrofolate Reductase (MTHFR) Mutation an Underlying Risk Factor?

The goal of this report is to present a case of coronavirus disease 2019 (COVID-19)-associated acute macular neuroretinopathy (AMN) with an underlying MTHFR mutation. A 36-year-old male presented to the emergency department with a sudden-onset paracentral scotoma in his left eye. Although optical coherence tomography (OCT) was normal initially, four days later, it revealed a hyperreflective band in the outer plexiform layer with disruption of the ellipsoid zone/interdigitation zone. On infrared imaging and en-face OCT, wedge-shaped lesions were detected around the fovea with their tip oriented toward the fovea. OCT angiography, fundus autofluorescence, fundus fluorescein angiography, and visual fields were performed. The patient was positive for COVID-19 infection. The absence of medical history and the negative results of blood tests led to a diagnosis of AMN associated with COVID-19. Genetic testing for coagulation disorders was scheduled and revealed a heterozygous mutation for MTHFR C677T and A1298C. This is the first case of AMN in a patient with COVID-19 infection and a double heterozygous mutation of the MTHFR gene. Infection is the most commonly reported association of AMN, while MTHFR mutation may represent an additional underlying risk factor. Microthrombosis and small-vessel occlusion are thought to be involved in the pathophysiology of AMN, and patients should be tested for COVID-19 because it may be the first manifestation of the infection.

Orbital Rhabdomyosarcoma Masquerading as a Dermoid Cyst: A Case Report and Review of the Literature.

The purpose of this report is to present a case of orbital rhabdomyosarcoma (RMS) masquerading as a dermoid cyst. A six-year-old boy with an unremarkable medical history presented in the outpatient department with a palpable mass in the superonasal region of the right orbit, which had rapidly grown in the past month. The most likely diagnosis was dermoid cyst and the patient was scheduled for surgical excision. A high index of suspicion was raised intraoperatively based on the appearance of the lesion due to the presence of a feeder vessel. The histopathology examination identified alveolar RMS. The patient was referred to a pediatric oncology department and commenced intravenous chemotherapy. RMS may masquerade as various conditions, including dermoid cysts and chalazion. A high index of suspicion should be raised in cases with rapidly growing lesions.

Macular Edema Following Silicone Oil Tamponade for Retinal Detachment: A Literature Review.

Macular edema (ME) is a major cause of reduced vision following intraocular surgery. Although the pathophysiology of ME is not completely understood, inflammatory mediators play a key role. The incidence of ME following pars plana vitrectomy with silicone oil tamponade varies between 13% and 27%. ME usually resolves spontaneously following silicone oil removal, but treatment may be required for resistant cases. In this review, the mechanisms of ME formation after pars plana vitrectomy, its incidence, and its possible therapeutic approaches are discussed.

Straatsma Syndrome: A Case Series.

The aim of this article is to report two cases of Straatsma syndrome, a rare disease characterized by the traditional triad of unilateral myelinated retinal nerve fibres, axial myopia, and amblyopia. The cases were a five-year-old and a three-year-old girl, both with unilateral myopia, visual acuity of 0.1 (decimal), and myelinated retinal nerve fibres in fundoscopy. Prescription of cycloplegic refraction findings and occlusion of the involved eye was attempted in both cases, but visual acuity did not improve. Poor-prognostic factors of Straatsma syndrome include a high degree of anisometropia and extensive myelination.

Long-term astigmatism changes following horizontal muscle recession: a prospective cohort study.

Strabismus surgery may cause refractive changes, particularly in astigmatism. The aim of this study is to evaluate those changes in astigmatism two and 12 months following unilateral recession of horizontal rectus muscles in children. The authors prospectively evaluated 66 children with esotropia or exotropia, that would undergo a unilateral recession strabismus surgery. Comparisons were made between the 66 eyes that would undergo strabismus surgery and the fellow unoperated 66 eyes of the same children. The 66 eyes that would undergo strabismus surgery were divided into medial (38 eyes) and lateral (28 eyes) rectus muscle subgroups, and further, into subgroups based on the astigmatism axis preoperatively (with-the-rule astigmatism: 35 eyes, no astigmatism: 20 eyes, oblique astigmatism: 10 eyes, against-the-rule astigmatism: 1 eye). All patients were examined one day preoperatively, and then, two and 12 months postoperatively. Paired tests were conducted, and the significant level was set to 0.05 or was adjusted for subgroups. Mean age of children included was 6.73 years (SD = 3.19). Mean astigmatism values preoperatively, 2 and 12 months postoperatively were 0.92D (SD = 0.95), 1.45D (SD = 1.04) and 1.50D (SD = 1.10), respectively, for the eyes that underwent strabismus surgery. A statistically significant mean increase of 0.58D in astigmatism values in the eyes that underwent strabismus surgery was observed 12 months postoperatively (p < .005). Astigmatism values in the eyes that did not undergo strabismus surgery did not statistically significantly change during the observation period. The increase of the absolute values of astigmatism in medial and lateral rectus muscle subgroups was similar, 0.59D (SD = 0.10) and 0.57D (SD = 0.11), respectively. For the eyes that had with-the-rule astigmatism and no astigmatism preoperatively, a statistically significant increase was shown 12 months postoperatively (0.64D and 0.66D respectively) (p < .005). Changes in astigmatism were observed in the eyes which underwent recession of horizontal rectus muscles compared to the fellow eyes, which did not undergo any intervention. An increase in cylindrical power was noted in the eyes that had with-the-rule and no astigmatism prior to surgery. This increase may be interpreted by the decreased tension of the recessed rectus muscle following strabismus surgery. Decreased forces, caused by the recessed horizontal rectus muscle, acting on the sclera on 180-degree meridian may lead to corneal flattening on this particular meridian and consequently, a corneal steepening on the 90-degree meridian. These changes seem to be stable during the first 12 postoperative months.

Fingolimod-associated macular edema: A case report of late onset.

INTRODUCTION: The authors present a case of a male with Multiple Sclerosis (MS) who developed unilateral Fingolimod-Associated Macular Edema (FAME) 10 years after initiating fingolimod therapy. By reporting this case study, the authors present a comprehensive review on FAME, its current incidence, and therapy options in MS patients. CASE DESCRIPTION: A 58-year-old Caucasian male patient was referred to the hospital with a history of MS. He was on fingolimod treatment for 10 years. The patient presented with a referring second episode of blurred vision in his left eye (OS). His best corrected visual acuity (BCVA) was 20/20 (right eye - OD) and 20/30 (OS). Dilated fundus examination of the OS revealed dull foveal reflex with retinal thickening. Spectral domain optical coherence tomography (SD-OCT) scan demonstrated increased central macular thickness of 459 µm, foveal cysts and subretinal fluid. Neurologists decided to discontinue fingolimod treatment based on the ophthalmological findings. Three months post fingolimod discontinuation, macular edema resolved and BCVA was 20/20 (OD) and 20/25 (OS). CONCLUSIONS: The authors report a case of late onset FAME. FAME may occur several years after starting fingolimod treatment and it should be part of differential diagnosis of blurred vision in patients receiving fingolimod. Both Microcystic Macular Edema secondary to MS and Macular Edema Associated with MS-induced Uveitis should always be excluded. Those two conditions, secondary to MS, might show the lack of drug effectiveness and the possible need for changing the existing therapy in order to prevent further disease progress.

Changes in astigmatism after horizontal muscle recession strabismus surgery: A retrospective cohort study.

Purpose: The aim of this study was to evaluate the changes in astigmatism after unilateral recession of horizontal rectus muscles in pediatric patients. Methods: The authors retrospectively evaluated the medical history of 52 children with esotropia or exotropia, that underwent a unilateral recession strabismus surgery. The intervention group consisted of the 52 eyes that underwent strabismus surgery, and the control group consisted of the other 52 fellow unoperated eyes of the same participants. The intervention group was divided into medial and lateral rectus muscle subgroups, and four subgroups based on the astigmatism axis preoperatively (A: with-the-rule astigmatism, B: no astigmatism, C: intermediate meridians, D: against-the-rule astigmatism). All patients were examined one day preoperatively, and then, six weeks postoperatively. Paired tests were conducted, and the significant level was set to 0.05 or was adjusted for subgroups. Results: A mean difference 0.43 D of astigmatism (95% CI: 0.27, 0.59) was observed after the surgery between intervention and control group (P < 0.001). Astigmatism change (postoperative - preoperative) in subgroup A was 0.50 D (P < 0.001) and in subgroup B was 0.75 D (P < 0.001). Moreover, astigmatism changes of 0.50 D were found in both lateral (P < 0.001) and medial rectus muscle group (P = 0.002). Conclusion: Strabismus surgery appears to be associated with alterations in astigmatism, and in particular increase in cylindrical power in the eyes that had with-the-rule astigmatism or no astigmatism preoperatively. Those changes should be considered when planning the operation, to avoid transforming clinically non-significant astigmatism into clinically significant.

COVID-19 in Ophthalmology. Current Disease Status and Challenges during Clinical Practice.

Purpose: The novel coronavirus disease 2019 (COVID-19) has raised a global public health concern. The purpose of this review is to summarize the evidence currently available on COVID-19 for its ocular implications and manifestations from both pathogenetic and clinical standpoints. Methods: For this narrative review, more than 100 relevant scientific articles were considered from various databases (PubMed, Google Scholar, and Science Direct) using keywords such as coronavirus outbreak, COVID-19, ophthalmology, ocular symptoms. Results:Daily healthcare both from patient and physician perspective, as well as on some guidelines regarding prevention and management have dramatically changed over the last few months. Although COVID-19 infection mainly affects the respiratory system as well as the gastrointestinal, cardiovascular, and urinary systems, it may cause a wide spectrum of ocular manifestations. Various challenges have to be faced to minimize exposure for both patients and physicians. Conclusion:The risk of COVID-19 infection should be considered and medical care should be prioritized for urgent cases. Appropriate management for patients with chronic cases that may result in adverse outcomes should not be neglected, while patients that can be monitored remotely should be identified.

Methods for depicting overlap in overviews of systematic reviews: An introduction to static tabular and graphical displays.

BACKGROUND AND OBJECTIVE: To introduce potential static tabular and graphical techniques for visually presenting overlap between systematic reviews (SRs) included in overviews of systematic reviews (OoSRs). METHODS: The graphical approaches described include Venn and Euler diagrams, as well as matrix-based, node-link, and aggregation-based techniques. We used fundamental concepts of mathematics from set and network theory to develop our novel graphical approaches. The graphical displays were created using R. RESULTS: Overview authors have the flexibility to choose from a variety of visualizations, depending on the characteristics of their study. If the OoSRs include few SRs, a Venn or an Euler diagram can be used. In case of OoSRs with more SRs, Upset plots, heatmaps, and node-link graphs are more appropriate for visualizing overlapping SRs. Stacked bar plots constitute an aggregation-based technique of illustrating overlap. Strengths and limitations of each graphical approach are presented. CONCLUSION: The degree of overlap should be explored for the entire study and for specific outcomes of interest. The proposed graphical techniques may assist methodologists and authors in identifying overlap, which in turn may improve validity and transparency in OoSRs. More research is needed to understand which technique would be most useful and easiest to understand.