Ocular Changes in Cystic Fibrosis: A Review.

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000-3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl-) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis.

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.

The Safety of Anti-VEGF Treatment, in the Context of the Retinal Nerve Fibre Layer, in Patients with Wet Age-Related Macular Degeneration: A Review.

Anti-vascular endothelial growth factor (VEGF) drugs are widely used in modern ophthalmology, especially in treating macular disorders like age-related macular degeneration or diabetic macular edema. Protocols for such treatments include repeated administration of intravitreal injections, with the volume of drug injected into the vitreous chamber seemingly high enough to cause an increase in intraocular pressure. Hence, questions might arise if such therapeutic approaches are safe for ocular tissue. Moreover, anti-VEGF compounds may theoretically harm the retinal nerve fibers due to the inhibition of VEGF and its neuroprotective effects. Thus, this manuscript aims to review the literature regarding studies evaluating the retinal nerve fiber layer (RNFL) in eyes receiving anti-VEGF treatment due to age-related macular degeneration. The RNFL was chosen as a subject of this review, as it is the innermost retinal layer exposed to the direct action of intravitreally administered drugs. The results of the available studies remain inconclusive. Most researchers seem to confirm the safety of the anti-VEGF treatment in wet age-related macular degeneration, at least regarding the retinal nerve fiber layer. However, some authors noticed that the influence of anti-VEGFs on RNFL could become apparent after more than thirty injections. Nonetheless, the authors of all studies agree that further, long-term observations are needed to help clinicians understand the effect of anti-VEGF treatment on the dynamics of changes in the thickness of retinal nerve fibers in patients with the wet form of age-related macular degeneration.

Early Optical Coherence Tomography Biomarkers for Selected Retinal Diseases-A Review.

Optical coherence tomography (OCT) is a non-invasive, easily accessible imaging technique that enables diagnosing several retinal diseases at various stages of development. This review discusses early OCT findings as non-invasive imaging biomarkers for predicting the future development of selected retinal diseases, with emphasis on age-related macular degeneration, macular telangiectasia, and drug-induced maculopathies. Practitioners, by being able to predict the development of many conditions and start treatment at the earliest stage, may thus achieve better treatment outcomes.

Visual outcomes in carotid stenosis patients treated using endarterectomy.

IntroductionCarotid arthrosclerosis can be a cause of visual impairment. It has been observed that carotid endarterectomy has a positive effect on ophthalmic parameters. The aim of this study was to evaluate the impact of endarterectomy on the optic nerve function.Materials and methods54 asymptomatic patients (19 women and 35 men - 108 eyes) with unilateral carotid stenosis >70% of internal carotid artery, were recruited to the study. All of them were qualified for the endarterectomy procedure. The whole study group underwent Doppler ultrasonography of internal carotid arteries and ophthalmic examination before the surgery, with 22 of them (11 women and 11 men) were examined after the endarterectomy. The ophthalmic examination included; distant best-corrected visual acuity, measurement of the intraocular pressure, electrophysiology (pattern visual evoked potentials), perimetry, and optical coherent tomography (the retinal nerve fiber layer thickness).DiscussionCarotid arteries supply brain and face with blood. Extensive research has observed a concomitant improvement in eyesight after enduring carotid endarterectomy in patients with artery stenosis. This effect was associated with a better blood flow in the ophthalmic artery and its branches, the central retinal artery and the ciliary artery; the major blood supply of the eye.ResultsThe present study proved that carotid endarterectomy has a positive impact on the function of the optic nerve. The visual field parameters and amplitude of pattern visual evoked potentials significantly improved. Preoperative and postoperative values of intraocular pressure and the retinal nerve fiber layer thickness remained stable.

Morphological and Functional Assessment of the Optic Nerve Head and Retinal Ganglion Cells in Dry vs Chronically Treated Wet Age-Related Macular Degeneration.

Purpose: The aim of the study comprised the anatomical and functional assessment of the optic nerves and macular ganglion cells in the population of patients with unilateral wet age-related macular degeneration (wAMD) and comparison of its results to those obtained from the fellow eye with non-advanced dry age-related macular degeneration (dAMD). Furthermore, we aimed to determine if the number of administered injections contributed to the potential differences between the examined eyes. Methods: The study was based on 104 eyes of 52 patients in a cross-sectional study. The eyes with chronically treated wAMD were the main subject of the study, while fellow eyes affected with non-advanced dAMD served as the control group. Primary morphological outcomes comprised differences in peripapillary retinal nerve fiber layer (RNFL) and GCC layers between the studied groups (treated and control). In turn, primary functional outcomes included differences in implicit times and amplitudes of the P100 wave of pattern visual evoked potentials (PVEP) and N95 wave of pattern electroretinogram (PERG) between treated and control groups. Results: We did not find any differences in total RNFL thickness between wAMD and dAMD groups. The number of injections only affected the RNFL in the nasal quadrant of the optic disc (p = 0.023). We did not find any differences regarding GCL thickness in both groups. In the study group, a longer implicit time of the P100 of PVEP (p = 0.014) and a shorter amplitude of the P50-N95 wave of PERG (p = 0.005) were detected. The total number of injections had no significant effect on these two values. Conclusion: We detected worse functional parameters of the optic nerve and retinal ganglion cells in eyes with wAMD, with lack of significant differences in anatomical (RNFL, GCL) parameters compared to the control group. However, the number of injections did not contribute to the differences found.

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

Diplopia and Optic Disc Edema as the Ocular Manifestations of COVID-19 in a Seven-Year-Old Child.

Serious ocular complications due to SARS-CoV-2 disease in children are rare. Herein, we present a case report of a seven-year-old patient, who was diagnosed with pediatric inflammatory multisystem syndrome (PIMS) due to COVID-19 and developed the ocular manifestations comprising diplopia and binocular optic disc edema. The patient condition improved within few weeks without any ocular sequels so far.

Methanol-induced optic neuropathy: a still-present problem.

Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol-formic acid-with the key enzyme of this process-cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30-40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide.

Examination of Inner Retinal Layers in Unilateral Wet Age-Related Macular Degeneration Treated with Anti-VEGF, Compared to Fellow Untreated Eyes.

The main aim of this study was to characterize the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in the macular area eyes affected by wet age-related macular degeneration (wAMD) treated with anti-VEGF and compare the results with the control of fellow untreated eyes affected by early stages of dry age-related macular degeneration (dAMD). Additionally, we aimed to estimate if the number of injections received and other factors, including age, best-corrected visual acuity (BCVA), or sex, may affect the differences in the obtained measurements of retinal nerve fiber layer thickness. We prospectively included 106 eyes of 53 patients with unilateral wet age-related macular degeneration. The fellow eyes with non-advanced dry age-related macular degeneration served as a control group in a cross-sectional study. RNFL and GCL in the macular region were evaluated using optical coherence tomography, with outcomes expressed as differences in the thickness of both examined layers between the study and control groups. We found thinner GCL in wAMD vs. dAMD (p < 0.001). In turn, the RNFL layer did not show any statistically significant differences between the two groups (p = 0.409). Similarly, we found a statistically significant correlation between the number of injections and the layer thickness (p = 0.106). Among all assessed parameters, age over 73 was the only factor significantly affecting the thickness of the retinal nerve fiber layer in both groups (p = 0.042). The morphology of the inner layers of the retina in dry and wet AMD seems to differ, possibly due to differences in the etiopathogenesis of these two forms of the disease. In our study, the retinal ganglion cell layer was thinner in the treated vs. fellow eye (with dry AMD), while the nerve fiber layer was not significantly different between the groups. The number of anti-VEGF injections had no effect on the thickness of the macular nerve fiber layer.

Ophthalmological problems in pregnancy - a review.

Pregnancy is associated with numerous changes affecting all organs. Ophthalmological changes in pregnant women are most often physiological and resolve spontaneously after delivery. However, the possibility of progression of previously diagnosed ophthalmic diseases or the occurrence of ophthalmological complications in the course of diseases characteristic for pregnancy should always be considered.

Skin Barrier Function in Patients with Primary and Secondary Sjögren's Syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease. A large percentage of patients with SS suffer from dry skin, the cause and pathogenesis of which in this group of patients remains obscure. The aim of the present study was to investigate skin barrier function in patients with SS. Measurements of transepidermal water loss (TEWL) and hydration of stratum corneum (corneometry, CM) were performed in 30 female patients with SS (17 with primary SS and 13 with secondary SS), 20 patients with atopic dermatitis (AD) and 14 healthy controls. There were no statistically significant differences in TEWL values between the three investigated groups, while CM values were significantly decreased in patients with AD when compared with patients with SS and the healthy controls. Based on the obtained results, skin barrier function and hydration in patients with SS showed no functional alterations.

Novel variants identified with next-generation sequencing in Polish patients with cone-rod dystrophy.

Purpose: The aim of this study was to identify the molecular genetic basis of cone-rod dystrophy in 18 unrelated families of Polish origin. Cone-rod dystrophy is one of the inherited retinal dystrophies, which constitute a highly heterogeneous group of disorders characterized by progressive dysfunction of photoreceptors and retinal pigment epithelium (RPE) cells. Methods: The study group was composed of four groups of patients representing different Mendelian inheritance of the disease: autosomal dominant (AD), autosomal recessive (AR), X-linked recessive (XL), and autosomal recessive or X-linked recessive (AR/XL). The combined molecular strategy included Sanger sequencing of the RPGR-ORF15 gene (three families with XL and three families with the AR/XL mode of inheritance), mutation-specific microarray analysis of the ABCA4 gene (five families with the AR mode of inheritance and two families with the AR/XL mode of inheritance), targeted next-generation sequencing (NGS) of inherited retinal disease-associated (IRD) genes (seven families with the AD mode of inheritance and five families with the AR mode of inheritance), and whole exome sequencing, performed in select families who had been mutation-negative in the analysis with the targeted NGS panel (one family with the AD mode of inheritance, one family with the AR mode of inheritance, and two families with the AR/XL mode of inheritance). Results: Based on this combined strategy, we managed to identify potentially causative variants in seven out of 18 families with CRD. Five of these variants are novel: c.3142_3143dupAA, p.(Glu1049Argfs*41) in the RPGR-ORF15 gene, two variants: c.1612delT, p.(Trp538Glyfs*15) and c.2389dupG, p.(Ile798Hisfs*20) in the PROM1 gene in one family, c.592A>C, p.(Ser198Arg) in the PRPH2 gene and the variant c.1691A>G, p.(Asp564Gly) in the ATF6 gene that we have already reported to be pathogenic. NGS on the IRD panel allowed the molecular basis of CRD to be identified in four out of 14 families with a total detection rate of 38%. WES allowed identification of the molecular genetic basis of CRD in one family. Conclusions: This is the first report on the spectrum of disease genes and pathogenic variants causing CRD in the Polish population. The study presents five novel variants identified in four genes and therefore, broadens the spectrum of probable pathogenic variants associated with CRD.

Levels of EGF and VEGF in patients with primary and secondary Sjögren's syndrome.

BACKGROUND: Aberrant angiogenesis plays a role in the pathogenesis of Sjögren's syndrome (SS). OBJECTIVES: The aim of this study was to compare the levels of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in stimulatory parotid saliva and in serum in healthy subjects (HS), patients with primary SS (pSS) and secondary SS (sSS) and to evaluate the expression of EGF, proangiogenic VEGF165 and antiangiogenic VEGF165 b mRNA isoforms. Additionally, we determined the salivary levels of serine/arginine splicing factor (SRSF1), which regulates VEGF165 and VEGF165 b expression. MATERIAL AND METHODS: The study comprised 34 women (16 with pSS and 18 with sSS) and healthy subjects for blood and saliva sampling. EGF and VEGF levels in saliva and serum and salivary SRSF1 levels were determined by enzyme-linked immunosorbent assay (ELISA). The expression of VEGF165 , VEGF165 b and EGF in peripheral blood mononuclear cells (PBMC) was evaluated by quantitative polymerase chain reaction (qPCR). RESULTS: There were no differences in the levels of EGF, VEGF, SRSF1 and in the expression of the EGF, VEGF165 and VEGF165 b between HS and SS patients, or between pSS and sSS patients. The salivary levels of VEGF165 and EGF were significantly higher in pSS, sSS and HS than serum levels. Levels of SRSF1 correlated positively with VEGF and EGF levels. Levels of EGF, VEGF and SRSF1 correlated with each other. CONCLUSIONS: The balance of VEGF isoforms is not disturbed in SS. Saliva is more sensitive for the detection of EGF and VEGF than serum, but salivary levels of those proteins are not representative for SS.

Eyelid arteriovenous malformation treated with pre-surgical embolization: A case report.

Background Arteriovenous malformations are potentially serious vascular anomalies that are rarely encountered in the eyelid and require a multidisciplinary approach. Objectives We would like to describe the technical and clinical aspects related to the treatment of palpebral arteriovenous malformation with selective embolization, followed by surgical resection. Methods A 40-year-old patient presented with an isolated high-flow palpebral arteriovenous malformation. Transarterial embolization, using a liquid embolic agent (PHIL™), was performed in this patient. Results Angiographic and clinical follow-up revealed good results with clinical regression of the mass. Conclusion Although endovascular treatment of palpebral arteriovenous malformations is technically challenging, good functional and cosmetic result was achieved. Arteriovenous malformation embolization using PHIL™ seems to be very effective and makes subsequent surgical procedure safe and feasible. Level IV Evidence obtained from multiple time series with or without the intervention, such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.

Serum ICAM-1, VCAM-1 and E-selectin levels in patients with primary and secondary Sjögren's syndrome.

BACKGROUND: Typical features of Sjögren's syndrome (SS) are severe xerostomia and xerophthalmia which are basic diagnostic criteria. OBJECTIVES: The aim of this study was to compare the serum levels of soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sE-selectin between primary (pSS), secondary (sSS) and healthy subjects (HS). We correlated these results with selected clinical parameters of disease activity and parameters of the severity of xerostomia and xerophthalmia. MATERIAL AND METHODS: The serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by enzyme-linked immunosorbent assay (ELISA) in 16 patients with pSS, 18 with sSS and 15 HS. Eye dryness and xerostomia were assessed by the Schirmer's test, the Fox test and the visual analogue scale (VAS). RESULTS: The levels of sICAM-1 in pSS and sVCAM-1 in sSS patients were significantly higher when compared to HS (p = 0.02 and p = 0.048, respectively). There were no differences between pSS and sSS. In pSS, sVCAM-1 correlated positively with VAS (rS = 0.52, p = 0.04) and the Fox test (rS = 0.66, p=0.01). In sSS, sE-selectin correlated positively with sICAM-1 (rS = 0.54, p = 0.01), the duration of the disease (rS = 0.51, p = 0.03) and negatively with the Schirmer's test (rS = 0.59, p = 0.04). sICAM-1 correlated positively with the erythrocyte sedimentation rate (ESR) value (rS = 0.59, p = 0.01). CONCLUSIONS: sVCAM-1 reflects xerostomia in pSS. sICAM-1 and sE-selectin may be additional parameters of sSS activity.

Ruthenium brachytherapy for uveal melanoma - single institution experience.

PURPOSE: The aim of this study was to report on results of uveal melanoma treatment with ruthenium-106 (106Ru) brachytherapy with long-term follow-up, in terms of local tumor control, eye retention rate, radiation retinopathy, and patients' survival. MATERIAL AND METHODS: Medical records of patients treated with ruthenium plaque due to uveal melanoma at the Department of Ophthalmology, Poznan University of Medical Sciences, Poland, between 1994 and 2014 were retrospectively reviewed. RESULTS: We identified 126 patients: 53 men, 73 women, mean age 60.04 years (range, 21-89). The largest basal diameter ranged from 4.04 mm to 18.9 mm (median, 10.67 mm), tumor height was 1.9 mm to 7.42 mm (median, 4.8 mm). Median scleral radiation dose was 570 Gy (range, 235-1,500 Gy), median apical dose 100 Gy (range, 60-129 Gy). Median follow-up was 66.5 months (range, 2-261 months). We noted a total of 19 (15%) recurrences. The actuarial rate of recurrence was 9.5% at 3 years, and 13.5% at 5 years postoperatively. Nine (7%) eye globes were lost, median time to enucleation was 5 years. The eye retention rate at 5 years was 92.7% and 81% at 10 years. Forty-three (34%) patients died before the end of the study, 24 (19%) of them due to metastatic disease. Metastatic death was related to: tumor size and TNM stage at presentation (p = 0.002 vs. p = 0.0006, respectively) but not to age, gender, and plaque dosimetry. CONCLUSIONS: 106Ru brachytherapy is an effective, globe sparing treatment that provides good tumor control and a high rate of survival. However, some ocular complications tend to appear late post-treatment, and therefore long-term follow-up is advised.

An update on thyroid-associated ophthalmopathy in children and adolescents.

BACKGROUND: Risk of developing thyroid-associated ophthalmopathy (TAO) in children and adolescents is similar or may be even slightly higher than in adults. The aim of this article is to review and summarize current knowledge regarding diagnostic and therapeutic measures in pediatric TAO. CONTENT: MEDLINE and EMBASE papers were searched using the terms 'pediatric Graves' ophthalmopathy' 'pediatric Graves' orbitopathy', 'thyroid-associated ophthalmopathy in childhood and adolescence' from the year 1970 to December 2015. SUMMARY: TAO usually accompanies hyperthyreosis in Graves' disease, but may also occur in patients with hypothyreosis due to chronic lymphocytic thyroiditis (Hashimoto's disease) or in euthyroid patients. Current information regarding epidemiology, pathogenesis, symptoms and treatment of TAO in children and adolescents is presented. The course of the disease is usually mild, eye disturbances often regress after restoring euthyroidism and a 'wait and see' policy is appropriate in the majority of patients. In rare cases, sight-threatening complications [dysthyroid optic neuropathy (DON) or corneal breakdown] may develop and immediate surgical intervention might become necessary. OUTLOOK: Close cooperation between pediatric endocrinologists and opthalmologists is extremely important to ensure best care and quality of life in patients with thyroid gland dysfunction. Further investigations on pathogenesis and course of TAO in children and adolescents should be performed for better management of this disease in this group of patients.