A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-KB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

Botulinum Toxin Injection for the Treatment of Third, Fourth, and Sixth Nerve Palsy: A Meta-Analysis.

The efficacy of botulinum toxin injection for the treatment of third, fourth, and sixth nerve palsy was evaluated. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar databases were searched. Data about the duration of palsy (acute vs chronic), cause of the palsy, type of toxin used, mean dose, and other background characteristics were collected. Outcome variables were success rate (defined by alleviation of diplopia or reduction in eye deviation) and standardized mean difference of prism diopter and abduction deficit before and after injection. The Joanna Briggs Institute checklist was implemented for the risk of bias assessment. The analysis included 38 articles, comprising 643 patients. The overall treatment success rate in acute and chronic nerve palsy was 79% and 33%, respectively. The success rate was not significantly different between different subgroups of age, type of botulinum toxin, pre-injection prism diopter, etiology of the palsy, duration of follow-up, and mean dose of botulinum toxin injection. However, in both acute and chronic palsy, diabetes etiology was accompanied by the highest success rate. Overall symptomatic response to botulinum injection was 84% (95% CI: 67% to 96%), whereas functional response was observed in 64% (95% CI: 47% to 79%) of the patients. The odds ratio for the success rate of treatment of palsies with botulinum toxin versus expectant management was 2.67 (95% CI: 1.12 to 6.36) for acute palsy and 0.87 (95% CI: 0.17 to 4.42) for chronic palsy. Botulinum toxin can be used for the treatment of acute third, fourth, and sixth nerve palsy, especially in patients with acute palsy and more severe tropia. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Recent advancements in nanomaterial-laden contact lenses for diagnosis and treatment of glaucoma, review and update.

Despite the existence of numerous eye drops in the market, most of them are not sufficiently effective because of quick clearance and the barriers within the eye. To increase the delivery of the drugs to the eye, various new formulations have been explored in recent decades. These formulations aim to enhance drug retention and penetration, while enabling sustained drug release over extended periods. One such innovative approach is the utilization of contact lenses, which were originally designed for cosmetic purposes and vision correction. Contact lenses have appeared as a promising formulation for ocular drug delivery, as they can increase the bioavailability of drugs in the eye and diminish unwanted side effects. They are specifically appropriate for treating chronic eye conditions, making them an area of interest for researchers in the field of ophthalmology. This review outlines the promising potential of nanomaterial-laden contact lenses for diagnosis and treatment of glaucoma. It classifies therapeutic approaches based on nanomaterial type, summarizes diagnostic advances, discusses improvement of contact lenses properties, covers marketing perspectives, and acknowledges the challenges of these innovative contact lenses for glaucoma management.

Determination of efficacy of repeated CXL and probable risk factors in patients with progressive keratoconus.

PURPOSE: To evaluate the efficacy of Repeated CXL (Re-CXL) and determine probable risk factors that lead to Re-CXL in patients with progressive keratoconus. METHOD: In this retrospective study, the medical records of patients who had been re-operated in our center between 2014 to 2020 due to progressive keratoconus were evaluated; seven eyes of seven patients had undergone Re-CXL procedure. Pre- and post-treatment variables were recorded and analyzed using IBM SPSS Statistics software. RESULTS: The mean interval between the 1st and 2nd CXL was 49.71 months (range 12-72 months). Out of 7 patients for whom Re-CXL was considered necessary, eye rubbing was detected in 6 patients. Six patients were very young with a mean age of 13 years at primary CXL and 16.83 years at Re-CXL. Visual acuity and astigmatism did not change significantly after the Re-CXL procedure (p-values = 0.18, 0.91, respectively). When measurements of these indices prior to Re-CXL and post Re-CXL were compared, K1 (p-value = 0.01), K2 (p-value = 0.01), Kmean (p-value = 0.01), and Kmax (p-value = 0.008) changed significantly. As to pachymetry (p-value = 0.46), it did not change significantly. Kmax value regressed in all eyes after Re-CXL. CONCLUSION: Re-CXL procedure was effective in halting the progression of disease. As to the risk factors, eye rubbed-related mechanism like eye rubbing and VKC, lower age, and pre-operative Kmax value > 58 D are the risk factors of Re-CXL procedure.

Therapeutic Implications of Curcumin in the Treatment of Inflammatory Eye Diseases: A Review.

Curcumin is the main active constituent of the medicinal plant Curcuma longa L., used traditionally as a medicinal spice in several ancient civilizations. Different preclinical and clinical studies support the anti-inflammatory properties of curcumin in various inflammatory diseases. As inflammation has an essential role in the pathophysiology of many ocular diseases, curcumin has been suggested as a promising therapeutic agent with anti-inflammatory properties. Based on the extent of experimental and clinical evidence, curcumin can exert protective effects against the corneal, uveal, retinal, optic nerve, orbital, and lacrimal gland inflammatory disorders. Herein, the available literature on the beneficial effects of curcumin in inflammatory eye diseases is reviewed. The limitations and future directions of these investigations are also discussed.

Optical coherence tomography angiography (OCT angiography) in anterior ischemic optic neuropathy (AION): A systematic review and meta-analysis.

PURPOSE: To summarize the evidence available on optical coherence tomography angiography (OCTA) in patients with anterior ischemic optic neuropathy (AION). METHODS: Systematic searches were conducted on PubMed, Embase, Web of Science, Scopus, Cochrane, and Google Scholar Databases. The quality assessment of the included studies was performed using Newcastle -Ottawa Scale. The data were extracted to an Excel sheet. Vessel density (VD) data were pooled by random effects model, presented as pooled percentage change (PPC), and weighted mean differences (WMD). Additional subgroup analysis was also conducted. RESULTS: In initial searches in online databases, we found 3535 citations, and after screening and checking the titles and abstracts, 26 articles were ultimately eligible for our meta-analysis. The overall PPC of Intra-optic-disc (IOD) VD (-10.73%; p = 0.017, I2 = 0.0%; p = 0.898) was lower than that of radial peripapillary (RP) VD (-17.57%; p < 0.001, I2 = 44.3%; p = 0.002). The overall PPC of peripapillary choroid VD (-6.99%; p < 0.001, I2 = 0.0%; p = 0.766) was significant, but noticeably lower than the pooled percentage change of RPVD and IOD VD. The WMD of RPVD was significant when non-affected fellow eyes were compared to the healthy subjects' eyes (-36.26; p < 0.001, I2 = 0.0%; p = 0.706). CONCLUSIONS: The central retinal artery and its branches might be the main vessels which are affected in AION. The superficial retina was more affected than choroid layer in AION. Also, radial peripapillary retinal nerve fibre layer was more affected than the IOD area. OCTA might be a suitable tool for prediction of AION in susceptible eyes.

Superior divisional third nerve palsy due to breast cancer metastasis to the orbital apex.

PURPOSE: To report a case of breast cancer with metastasis to the orbital apex with manifestation of superior divisional third nerve palsy. CASE DESCRIPTION: A 40-year-old female, a known case of breast cancer diagnosed 3 years ago, referred to our neuro-ophthalmology clinic with chief complaint of ptosis and diplopia. In ophthalmic examination, visual acuities of both eyes were 20/20 and there was no significant finding in the anterior and posterior segment ophthalmic examination. There was left eye ptosis with MRD1 of 2 mm. In ocular movement examination, there was limitation of motion in supraduction (-2 to -3) of the left eye. Orbital MRI with contrast was requested for the patient which demonstrated a lesion in the orbital apex of the left eye. At the end, the patient was diagnosed as having superior divisional third nerve palsy. Orbital radiotherapy was recommended for the patient. CONCLUSION: In a patient with breast cancer who presents with diplopia, metastasis to the orbital apex with manifestation of divisional third nerve palsy should be kept in mind, and appropriate orbital imaging should be considered.

Serum Selenium Levels in Patients With Graves Disease With or Without Thyroid Ophthalmopathy.

BACKGROUND: Graves disease is one of the most common autoimmune thyroid diseases. Thyroid has the highest concentration of selenium (Se) in the body. Se plays a crucial role in the functioning of some thyroid enzymes; however, there are controversial results regarding the administration of serum Se levels in patients with Graves disease. METHODS: In this study, patients with Graves disease with orbitopathy (GO group) or without orbitopathy (GD group) were recruited. Healthy individuals without a history of any disease were enrolled as the control group. Serum Se and thyroid hormone levels, including T3, T4, and thyroid-stimulating hormone (TSH), were measured using atomic absorption and radioimmunoassay techniques, respectively. RESULTS: In this cross-sectional study, 60 and 56 patients and 58 healthy subjects were included in the GO, GD, and control groups. Serum Se levels in the GO, GD, and control groups were 94.53 ± 25.36 µg/dL, 96.82 ± 30.3 µg/dL, and 102.55 ± 16.53 µg/dL, respectively (P = .193). There was a reverse association between the serum Se level and thyroid hormones, including T3, T4, and TSH, in the GO group. However, serum Se levels exhibited a significant reverse association with T4 and TSH hormones but not with T3 in the GD group. CONCLUSION: Our results showed no significant differences in the serum Se levels in the GO and GD groups compared with that in the control group. In addition, we did not detect any significant difference in the serum Se levels between the GO and GD groups.

A Review on the Application of Stem Cell Secretome in the Protection and Regeneration of Retinal Ganglion Cells; a Clinical Prospect in the Treatment of Optic Neuropathies.

PURPOSE: Retinal ganglion cells (RGCs) are one the most specialized neural tissues in the body. They transmit (and further process) chemoelectrical information originating in outer retinal layers to the central nervous system. In fact, the optic nerve is composed of RGC axons. Like other neural cells, RGCs will not completely heal after the injury, leading to irreversible vision loss from disorders such as glaucoma that primarily affect these cells. Several methods have been developed to protect or regenerate RGCs during or after the insult has occurred. This study aims to review the most recent clinical, animal and laboratory experiments designed for the regeneration of RGC that apply the stem cell-derived secretome. METHODS: We extracted the studies from Web of Science (ISI), Medline (PubMed), Scopus, Embase, and Google scholar from the first record to the last report registered in 2022, using the following keywords; "secretome" OR "conditioned medium" OR "exosome" OR "extracellular vesicle" AND "stem cell" AND "RGC" OR "optic neuropathy". Any registered clinical trials related to the subject were also extracted from clinicaltrial.gov. All published original studies that express the effect of stem cell secretome on RGC cells in optic neuropathy, whether in vitro, in animal studies, or in clinical trials were included in this survey. RESULTS: In this review, we provided an update on the existing reports, and a brief description of the details applied in the procedure. Compared to cell transplant, applying stem cell-derived secretome has the advantage of minimized immunogenicity yet preserving efficacy via its rich content of growth factors. CONCLUSIONS: Different sources of stem cell secretomes have distinct implications in the management of RGC injury, which is the main subject of the present article.

Optic Neuropathy following Botulinum Toxin Injection into the Medial Rectus Muscle for Diplopia.

Purpose: To report a case of optic neuropathy (ON) following botulinum toxin A (BTA) injection into the medial rectus muscle. Case Report: We describe a 37-year-old man with unilateral ON after a BTA injection into the left medial rectus for treatment of traumatic sixth nerve palsy. Oral prednisolone was prescribed for 14 days. After two weeks, his visual acuity returned to 20/20. Conclusion: Botulinum toxin-induced neuropathy is a rare and vision-threatening complication of BTA. In patients with recent injection of BTA who present with visual complaints, botulinum toxin-induced neuropathy should be considered.

Fungal exopolysaccharides: Properties, sources, modifications, and biomedical applications.

Fungal exopolysaccharides (EPSs) are natural biopolymers with diverse potential applications in the biomedical, packaging, cosmetic, and food industries. Fungal EPSs are easy to extract and purify polysaccharides that are biodegradable, biocompatible, with low immunogenicity, bioadhesion ability, antibacterial activity, and contain different reactive groups such as hydroxyl, carboxyl, and amine for chemical modifications. Despite fast progress in identifying and characterization fungal EPSs for biomedical applications, i.e., wound healing, drug, and gene delivery, only a few products have been commercialized based on fungal EPSs. This review critically discusses potential biomedical applications of fungi sourced EPSs in tissue engineering (TE), drug and gene delivery.

The prevalence of refractive error in schoolchildren.

CLINICAL RELEVANCE: Information on the refractive error prevalence in school-aged children will result in delivering the optimal eye health service to this group. BACKGROUND: Understanding the prevalence of refractive error in school-aged children is crucial to reduce the consequences of uncorrected refractive error. This study aims to investigate the prevalence of refractive error among school-aged children in Shiraz, Iran. METHODS: In this cross-sectional population-based study, 2001 schoolchildren aged 6-12 years participated. All participants underwent cycloplegic refraction. Spherical equivalent (SE) of -0.50 dioptre or more was considered as myopia, SE of +2.00 dioptre or more as hyperopia, and astigmatism as cylinder power of 0.75 dioptre or more. The difference of 1.00 dioptre or more between two eyes defined as anisometropia. RESULTS: The prevalence of myopia was 11.6% (95% confidence interval [CI]: 10.2-13.1%), hyperopia 6.7% (95%CI: 5.6-7.9%), and astigmatism 28.9% (95%CI: 26.9-31.0%), out of which 82.1% had with the rule astigmatism. Anisometropia was detected in 4.0% (95%CI: 3.2-5.0%) of children. Astigmatism and anisometropia were significantly higher in boys (p < 0.001, p = 0.03 respectively). The SE decreased significantly with increasing age (p < 0.001) indicating an increase in myopia with age. In addition, the rate of myopic astigmatism increased with age (p < 0.001). Among studied schoolchildren 97.0% could achieve the best-corrected visual acuity of 6/6 and 3.0% could not in the better eye. CONCLUSION: Astigmatism was the most common refractive error among primary school children. The prevalence of myopia was relatively higher than other studies conducted in Iran, and it increased with age. These results may highlight the role of lifestyle changes and increased near work activities on the myopic shift in school-aged children. The findings provide information for screening programmes in school-aged children.

Long-term outcome of refractive errors in patients with congenital blepharoptosis who have undergone ptosis surgery.

CLINICAL RELEVANCE: Ptosis surgery induces some changes in pre-existing refractive errors and astigmatism. Monitoring refractive outcomes, planning of vision rehabilitation, and amblyopia treatment may be required following ptosis surgery. BACKGROUND: The few studies published on the outcomes of refractive error after ptosis surgery have been controversial. The aim of this study was to evaluate long-term outcomes of refractive error in patients with congenital blepharoptosis who had undergone ptosis surgery. METHODS: Patients with congenital blepharoptosis who had undergone ptosis surgery were enrolled in the study. Data on pre- and post-operative refractive errors, marginal reflex distance 1 (MRD1), and levator function were obtained. The data from fellow eyes were used as the control. RESULTS: The mean patient age of patients undergoing ptosis surgery was 19.8 ± 8 years. The mean follow-up time (time between the operation and post-up measurements) was 4.7 ± 2.1 years with a range of 2-10 years. There were no significant differences in mean refractive changes, being 0.53 ± 0.40D vs. 0.36 ± 0.45D in sphere (p = 0.19) and 0.48 ± 0.56 vs. 0.30 ± 0.23 in cylinder (p = 0.17) in operated and control eyes, respectively. Astigmatism change was, however, significantly higher in the operated eyes with an MRD1 change of ≥2.5 mm (0.84 ± 0.66 vs. 0.27 ± 0.39, p = 0.024). The changes in astigmatism in the operated eyes had a significantly positive correlation with the changes of MRD1 (r = 0.497, p = 0.019). Vectorial analysis showed no significant difference between the changes in astigmatism of the operated and control eyes (0.58 *48º vs. 0.45*53º, respectively). CONCLUSION: Spherical power of the eyes of patients with congenital ptosis who undergo ptosis surgery does not change. A significant change in astigmatism can be anticipated in eyes with more than 2.5 mm change in MRD1. There is an association between change in astigmatism and MRD1 following ptosis surgery.

Consanguinity and Increased Risk of Congenital Ptosis: A Case-Control Study from Southern Iran.

Purpose: To assess consanguinity as a probable risk factor for congenital ptosis. Methods: In this case-control study, 97 patients with congenital ptosis and 97 participants as the control group were included. The age, sex, and residence area of the control group were matched with the cases. The inbreeding coefficient (F) was calculated for each participant, and the mean of the inbreeding coefficient (α) was calculated for each group. Results: The prevalence of consanguineous marriage in parents of cases with congenital ptosis and those of the control group was 54.6% and 30.9%, respectively (P < 0.002). The mean of the inbreeding coefficient (α) in patients with ptosis was 0.026, whereas it was 0.016 in the control group (T = 2.51, degree of freedom = 192, P = 0.0129). Conclusions: The rate of consanguineous marriage was significantly higher among the parents of patients with congenital ptosis. It implies a probable recessive pattern in the etiology of congenital ptosis.

Corneal Biomechanical Changes after Corneal Cross-Linking in Patients with Keratoconus.

Purpose: To evaluate the changes in biomechanical properties of the cornea using the Corvis ST device after the treatment of keratoconus patients with ultraviolet-A/riboflavin corneal cross-linking (CXL). Methods: Thirty-seven eyes from 37 consecutive patients with progressive keratoconus were included in this prospective observational case series. Corneal biomechanical parameters including the length of the applanated cornea (L1 and L2), corneal movement velocity during applanation (V1 and V2) at the moment of the first and second applanation, deformation amplitude (DA), distance between bending points of the cornea points of the cornea (PD), and concave radius of curvature (R) at the point of the highest concavity were recorded using the Corvis ST at baseline, 3 months, and 1 year after CXL. Results: The mean age of the patients was 23.27 years (range, 19-31 years). Among CorVis ST corneal biomechanical parameters, L1, DA, PD, and R at the point of the highest concavity did not change significantly. The length of the applanated cornea at the moment of second applanation (L2) showed a significant change 3 months after CXL, but no significant difference was found between the 3-month and 1-year values of this parameter. Corneal movement velocity during applanation (V1 and V2) did not change 3 months after doing CXL, but the changes in these parameters were significant 1 year after CXL. Conclusions: Although the CorVis ST device may detect changes in some biomechanical properties of cornea after the treatment of keratoconus patients with CXL, many parameters remain unchanged, and this device cannot readily be used to find the effects of CXL.