The genetic differences between types 1 and 2 in von Hippel-Lindau syndrome: comprehensive meta-analysis.

BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are at risk of developing tumors in the eye, brain, kidney, adrenal gland, and other organs based on their gene mutations. The VHL tumor suppressor gene contains pathogenic variants responsible for these events. This meta-analysis aims to investigate the genetic differences among the various types of VHL syndrome and their correlation with the location of mutations (exons and domains) in the VHL gene. METHOD: Papers eligible for publication until September 2023 were identified using the electronic databases of PubMed, Google Scholar, Scopus, and EMBASE. The Random Effect model was utilized to evaluate the genetic differences between type 1 and type 2 VHL syndromes. RESULTS: The prevalence of missense mutations (MSs) was found to be 58.9% in type 1, while it was 88.1% in type 2. Interestingly, the probability of observing MSs in type 1 was 0.42 times lower compared to type 2. The mutation hotspots of the VHL gene were R167Q/W, Y98H, R238W, and S65L, respectively. Although type 2 had a high presentation of Y98H and R238W, it did not have a higher S65L than type 1. The analysis demonstrated a statistically significant higher prevalence of truncated mutations (PTMs) in type 1. Among type 1, large/complete deletions (L/C DELs) were found in 16.9% of cases, whereas in type 2 only 3.7%. This difference was statistically significant with a p-value < 0.001. Overall, the probability of identifying mutations in domain 2 compared to domain 1 was found to be 2.13 times higher in type 1 (p-value < 0.001). Furthermore, the probability of detecting exon 1 in comparison with observing exon 2 in type 1 was 2.11 times higher than type 2 and revealed a statistically significant result (p-value < 0.001). The detection of exon 2 was 2.18 times higher in type 1 (p-value < 0.001). In addition, the likelihood of discovering exon 2 compared with others was significantly lower in type 1 compared with type 2 VHL (OR = 0.63, p-value = 0.015). CONCLUSIONS: We have revealed a comprehensive genetic difference between types 1 and 2 of VHL syndrome. The significant differences in MS, PTMs, L/C DELs, and the location of the mutations between type 1 and type 2 VHL patients in the Asian, European, and American populations emphasize the genetic heterogeneity of the syndrome. These findings may pave the way for the diagnosis, treatment, and further investigation of the mechanisms behind this complex genetic disorder.

Diagnosis and Treatment of Lacrimal Gland Prolapse: A Narrative Review.

BACKGROUND: Lacrimal gland prolapse (LGP) is considered to be one of the causes for upper eyelid contour abnormality that should be recognized and treated properly to yield satisfactory outcomes in blepharoplasty. To describe current findings about the prevalence, pre- and intraoperative diagnosis of LGP and its treatment options. METHODS: PubMed and Google Scholar were thoroughly searched for articles published describing the diagnosis and treatment of LGP. RESULTS: The reported prevalence of LGP by various authors varies between 10 and 60% based on their preoperative or intraoperative reports. Techniques such as dacryoadenopexy, modified dacryoadenopexy, and dacryoplasty have been described to secure the prolapsed lacrimal gland back into its original position. Additionally, creating a Whitnall's barrier has also been suggested as a method to reposition the gland. While all these surgical procedures have shown promising immediate results, there is a lack of published data on their long-term outcomes. CONCLUSION: Diagnosis and proper treatment of LGP could enhance the cosmetic results of upper eyelid blepharoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intradermal methylene blue analgesic application in posthemorrhoidectomy pain management: a randomized controlled trial.

Introduction: Unbearable post-hemorrhoidectomy pain is a well-documented challenge, significantly impacting patient well-being and satisfaction after surgery, often influencing patients to decline in undergoing this procedure. It is widely recognized that methylene blue has an effect of reducing inflammation and pain by reduces the production of nitric oxide and inhibiting the action potentials production in nerves. This study aims to explore the potential benefits of postoperative regional administration of methylene blue in providing extended relief from post-hemorrhoidectomy pain. Methods: This study included 97 patients aged 18-75 undergoing hemorrhoidectomy for stage III or IV hemorrhoids. A double-blind, randomized controlled trial compared postoperative intradermal injections of 1% methylene blue to 0.5% Marcaine as the control group. Two-week follow-up assessed pain. Statistical analysis, adherence to ethical standards, and registration were conducted. Result: No significant differences were found in baseline demographics, surgical parameters, or complications between the Methylene Blue and control groups. Intervention group remained lower in mean pain score until the 12th day. Methylene blue group reported significantly lower postoperative pain scores from days 1 to 7, with no significant differences afterward. Conclusion: This ongoing randomized controlled trial reveals the potential analgesic benefits of intradermal injection 1% methylene blue. It demonstrates comparable efficacy in reducing post-hemorrhoidectomy pain, with negligible side effects and complications.

Assessment of the relationship between structural and functional tests in patients with idiopathic intracranial hypertension.

PURPOSE: To assess the relationship between structural and functional tests in mild and moderate idiopathic intracranial hypertension (IIH). METHODS: Patients with mild and moderate IIH and a control group were enrolled. Best-corrected visual acuity (BCVA), macular ganglion cell layer (MGCL) thickness, peripapillary retinal nerve fiber layer (pp RNFL) thickness, perimetric mean deviation (MD), and photopic negative responses (PhNR) of the electroretinogram were recorded. The associations between structural (pp RNFL and MGCL thickness) and functional (PhNR amplitude, MD and BCVA) parameters were assessed. RESULTS: 154 eyes from 78 subjects (74 eyes from IIH patients and 80 eyes from healthy subjects) were included in this comparative observational study. The MGCL thickness, VA, pp RNFL, and PhNR base-to-trough (BT) amplitude were significantly worse in moderate IIH. The BCVA and MD were associated with MGCL thickness only in moderate IIH. The relationship between MD and MGCL thickness started when MD fell below -5.7 dB. CONCLUSIONS: The association between functional and structural parameters varies between mild and moderate IIH. The MD and MGCL thickness outperformed in assessing disease severity in mild and moderate IIH, respectively. The association between MD and MGCL thickness could be considered in IIH severity categorization.

Oral supplementation with crocin (a constituent of saffron) in subjects with cigarette smoking: a clinical trial.

Smoking is one of the main causes of death in the world. Cigarette use is related with various components of metabolic syndrome (e.g., insulin resistance, raised blood pressure, dyslipidemia, oxidative stress, inflammation state) and psychiatric disorders. This study was conducted to determine the effect of crocin (Cro) supplementation on nicotine dependence, anxiety, depression, and metabolic indices in smokers. A total of 50 smokers were selected and randomly categorized into two groups (crocin and placebo). The intervention group received crocin (30 mg per day; n = 25) and placebo (containing Avicel; n = 25) once a day. The primary (nicotine dependence, depression, and anxiety inventory) and secondary (metabolic indices) outcomes were assessed at the start of the intervention and after the 3 months. Multiple linear regression models were used to assess the treatment effects on the outcomes adjusting for confounding variables. The primary outcome results such as nicotine dependence, depression, and anxiety inventory did not have a significant difference among the intervention groups (P > 0.05). Also in the secondary outcomes, fasting plasma glucose (FPG), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) levels did indicate a significant difference by Cro intervention (ß - 3.27 mg/dL; 95% CI, - 5.23, - 1.31; P = 0.002; ß - 0.76 µIU/mL; 95% CI, - 1.38, - 0.15; P = 0.01; ß - 0.18; 95% CI, - 0.29, - 0.07; P = 0.002), respectively. There were also significant reductions in serum levels of high-sensitivity C-reactive protein (hs-CRP) (ß - 0.72 mg/L; 95% CI, - 1.37, - 0.07; P = 0.03), compared with the placebo. Cro intake may have favorable effects on the level of FPG, insulin, HOMA-IR, and hs-CRP in smokers. However, due to the small sample size and limited scientific reports on smokers, further studies are necessary. ClinicalTrial.gov Identifier: IRCT20170420033551N11.

Assessing the success rate of treatment in simple and complex congenital nasolacrimal duct obstruction: a systematic review and meta-analysis.

PURPOSE: To assess and compare the success rate (SR) of probing and intubation in patients with congenital nasolacrimal duct obstruction (CNLDO). METHODS: We conducted a literature search for identifying relevant studies published in English using PubMed, Google Scholar, Scopus, and Web of Science databases from the date of inception to Feb 2023. After extracting data, the SR was compared between the study groups: simple and complex CNLDO. To compare the treatment outcome, the mean difference of the SR was considered as the effect size. Random effects model or fixed effects model were performed for statistical inferences. RESULTS: A total of 21 studies were eligible to be analyzed. The pooled SR of treatment was 88% in simple, and 57% in complex CNLDO. Exerting intubation in increased the SR from 87% (SR of probing) to 92% in simple CNLDO which was not significant. However, compared to probing, intubation has a significantly higher SR in complex CNLDO (46 to 82%). While the SR of probing was significantly lower in complex CNLDO, the difference between the SR of intubation was not significant between groups. Although increasing the age does not have an adverse effect on the SR in simple CNDLO, it causes a significant decrease in the SR of complex group. CONCLUSION: This study revealed that even though the addition of NLD intubation does not provide significant benefits beyond probing alone for patients with simple CNLDO, in children with complex CNLDO, NLD intubation should be considered as a primary treatment due to its substantial increase in surgical success rates. Delaying the treatment would increase its success in patients with complex but not the simple CNLDO.

Guanylate cyclase-C Signaling Axis as a theragnostic target in colorectal cancer: a systematic review of literature.

Introduction: Colorectal cancer (CRC) is a devastating disease that affects millions of people worldwide. Recent research has highlighted the crucial role of the guanylate cyclase-C (GC-C) signaling axis in CRC, from the early stages of tumorigenesis to disease progression. GC-C is activated by endogenous peptides guanylin (GU) and uroguanylin (UG), which are critical in maintaining intestinal fluid homeostasis. However, it has been found that these peptides may also contribute to the development of CRC. This systematic review focuses on the latest research on the GC-C signaling axis in CRC. Methods: According to the aim of the study, a systematic literature search was conducted on Medline and PubMed databases. Ultimately, a total of 40 articles were gathered for the systematic review. Results: Our systematic literature search revealed that alterations in GC-C signaling compartments in CRC tissue have demonstrated potential as diagnostic, prognostic, and therapeutic markers. This research highlights a potential treatment for CRC by targeting the GC-C signaling axis. Promising results from recent studies have explored the use of this signaling axis to develop new vaccines and chimeric antigen receptors that may be used in future clinical trials. Conclusion: The findings presented in this review provide compelling evidence that targeting the GC-C signaling axis may be an advantageous approach for treating CRC.

The Prevalence of Undiagnosed Ptosis Among Candidates for Upper Eyelid Blepharoplasty.

Background: Because upper eyelid blepharoplasty has become a popular aesthetic facial surgery, surgeons should be aware that age-related changes in the eyelid are not confined to skin laxity and orbital fat prolapse. Objectives: This study was designed to assess the prevalence of undiagnosed ptosis among blepharoplasty candidates as one of the causes of unsatisfactory surgical results. Methods: From December 2018 to December 2022, blepharoplasty candidates were meticulously assessed for their upper eyelid and eyebrow position. Patients who were aware of their ptosis were excluded, and the other patients were classified as mild, moderate, or severe ptotic based on margin reflex distance 1. The eyebrow height was also assessed in the mid-pupillary line to assess the relationship between the severity of ptosis and eyebrow asymmetry. Results: The authors found that 13.7% of the 2530 blepharoplasty candidates in this study had undiagnosed ptosis. Most of these patients had mild ptosis (85.5%), and they were significantly older than nonptotic patients. The rate of prevalence of ptosis was significantly higher in patients with eyebrow asymmetry (75.3% vs 3.7%); however, the severity of ptosis was not associated with the severity of eyebrow asymmetry. Conclusions: Ptosis should be cautiously looked for and addressed for treatment in candidates for upper blepharoplasty. In most patients with masked ptosis, the severity of eyelid drooping is mild and could remain undiagnosed until after the surgery and cause unsatisfactory aesthetic results. The presence of eyebrow asymmetry could be a key feature to unmask an undiagnosed ptosis.

Identification and genotyping of Acanthamoeba spp. in the water resources of western Iran.

Background: Acanthamoeba spp. is opportunistic amoeba that resides in water, soil, and air. Some pathogenic genotypes of the genus of Acanthamoeba can cause granulomatous amoebic encephalitis (GAE) in people with a defective immune system. The parasite can also cause Acanthamoeba keratitis (AK) among contact lens users. This study was conducted to isolate and identify the Acanthamoeba genotypes in water resources in Lorestan province, western Iran. Methods: Collected 72 water samples from surface and groundwater (springs and aqueducts) in Lorestan province. Samples were filtered and cultured in non-nutrient 1.5% agar medium covered with Escherichia coli (E. coli) at 25 °C. DNA extraction was done and the PCR reaction was performed to detect the Acanthamoeba spp. The positive PCR products were sequenced to determine the genotypes of Acanthamoeba. Results: Out of 72 examined water samples, 23.61% were positive for Acanthamoeba sp. by PCR. From PCR-positive samples, 8 (47.05%) samples were T4 genotypes and others were other Acanthamoeba genotypes (T1-T23). Therefore, approximately half of the genotypes belong to the pathogenic T4 genotype. Conclusions: The water examined samples in western provinces of Iran have the potential risk factor for public health. Therefore, the efforts of healthcare providers are needed to identify, train, and prevention from human infections.

Pediatric rhegmatogenous retinal detachment: A meta-analysis of clinical features, surgical success rate, and prognostic factors.

Pediatric rhegmatogenous retinal detachment (RRD) is an issue of debate regarding its surgical outcomes and prognosis because of diagnosis delay, more complex etiological factors, and a higher prevalence of postoperative complications. This meta-analysis aims to evaluate the anatomical and visual outcomes of pediatric RRD and the factors that influence the treatment results. This is the first meta-analysis on this subject. We searched the relevant publications in the electronic databases of PubMed, Scopus, and Google Scholar. Eligible studies were included in the analysis. Anatomical success after one surgery and the final rates of success were estimated. Subgroup analysis was performed to find the rate of success in patients with different prognostic factors. This meta-analysis showed that the total rate of success after one surgery was about 64%, which implies that performing the first surgery was enough to get anatomical reattachment in most of the patients. The final anatomical rate of success was about 84%. In terms of visual acuity, the pooled results revealed statistically significant (P < 0.001) improvement in postoperative vision, with a 0.42 reduction in log of minimum angle of resolution (logMAR). The final rate of success was significantly lower in eyes with proliferative vitreoretinopathy (PVR) (about 25% lower in eyes with PVR, P < 0.001) and in the presence of congenital anomalies (about 36% lower in congenital cases, P = 0.008). Myopic RRD had a significantly better anatomical success rate. In conclusion, this study shows that there is a high chance of anatomical success after pediatric RRD treatment. The presence of PVR and congenital anomalies was associated with a poorer prognosis.

NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY ASSOCIATED WITH IPSILATERAL HYPOPLASTIC INTERNAL CAROTID ARTERY.

BACKGROUND: Vascular insufficiency of the optic nerve head is the cause of nonarteritic ischemic optic neuropathy (NAION). Carotid artery abnormalities are now considered as a predisposing factor for developing NAION. In this report, we present a case of NAION associated with ipsilateral internal carotid artery hypoplasia. METHODS: A 69-year-old female with decreased vision in her right eye due to NAION was evaluated. the magnetic resonance imaging showed a considerably smaller left internal carotid artery than the right side. The magnetic resonance angiography confirmed the disparity and perfusion abnormalities of intracranial carotid arteries. RESULTS: The diagnosis of left internal carotid artery hypoplasia was made and verified by depicting a left side small carotid canal on the computed tomography scan. CONCLUSION: This report suggests that internal carotid artery hypoplasia could be associated with NAION.

Bilateral Vision Loss in an Adult Patient with Woakes' Syndrome: An Unprecedented Case.

Purpose: To report a rare case of Woakes' syndrome presented with bilateral vision loss. Methods: A 28-year-old male with a 1-year history of vision loss in the left eye was referred to the neuro-ophthalmology clinic after sudden vision loss in his right eye. A detailed review of clinical findings and the presumed pathophysiological basis of vision loss was performed. Results: Neuroimaging revealed bilateral massive nasal polyps, sphenoid sinus mucocele formation, and optic nerve dehiscence inside the sphenoid sinus. The vision in the right eye was restored after pulse corticosteroid therapy; however, the left eye remained severely visually compromised even after nasal polypectomy and mucocele drainage. Conclusion: Sinonasal disorders should be sought for patients with unexplained vision loss, as prompt intervention could be vision-saving in these patients.

A meta-analysis of different von Hippel Lindau mutations: are they related to retinal capillary hemangioblastoma?

Retinal capillary hemangioblastomas (RCH) is a benign tumor that represents the initial manifestation in roughly half of Von Hippel Lindau (VHL) patients. They may also occur sporadically without systemic involvement. A first meta-analysis study was investigated to estimate the prevalence of Retinal capillary hemangioblastoma (RCH) in Von Hippel Lindau (VHL) syndrome, and its relation to type and location of mutations in VHL gene. The electronic databases of PubMed, Scopus, Embase, and Google Scholar were utilized to find eligible papers published up to May 2020. Lastly, after the different prevalence of RCH in Europe compared to other continents was noted, we decided to consider European and non-European patients separately. The Random effect model was used to evaluate the relation between developing RCH and types of mutations. The overall prevalence of RCH among VHL patients is about 47%. The prevalence of RCH was significantly higher in Europe in comparison with non-Europeans (p value < 0.001). Overall, the differences between the prevalence of RCH among different mutation types were not statistically significant. However, in Europe, the prevalence of RCH was significantly higher in patients with truncation mutation (p value = 0.007). In Europe, the RCH in VHL patients who had a mutation in exon 2 was significantly lower in comparison with exon 1 (p value = 0.001); but in non-Europeans, the prevalence of RCH in VHL patients that involved exon 2 was significantly higher in comparison with VHL patients with a mutation in exon1 (p value = 0.012). The highest risk of developing RCH was reported among Europeans. Overall, this study showed that the prevalence of RCH in VHL syndrome is not related to type or location of mutations and difference of RCH prevalence is probably depends on other genetic or environmental factor that should be considered in subsequent studies.

Paediatric myopia shift during the COVID-19 pandemic home quarantine: a systematic review and meta-analysis.

BACKGROUND: Outdoor activities were restricted during the COVID-19 outbreak, although digital learning grew. Concerns have been raised about the impact of these environmental changes on myopia status. This research aimed to examine myopia shift during the COVID-19 pandemic and offer the community evidence-based data. METHODS: The literature search was undertaken in PubMed, SCOPUS, Science Direct, Web of Science and Google Scholar databases on published papers before 17 May 2022. The main outcome was mean spherical equivalent refraction (SER) before, at the onset and at the end of follow-up during the COVID-19 pandemic. RESULTS: Among 518 articles, 10 studies were included in the meta-analysis. The mean SER differences during the COVID-19 pandemic follow-up (mean follow-up time was 10 months) compared with before the pandemic was 0.15 dioptre (D) (95% CI -0.39 to 0.69, p=0.58). After age adjustment using meta-regression, the mean SER differences during the COVID-19 follow-up compared with before the pandemic was - 0.46 D (95% CI -0.59 to -0.34, p<0.001). Over the mean follow-up time during the COVID-19 pandemic, the SER mean difference was -0.55 D (95% CI -0.78 to -0.32, p<0.001), showing that the mean SER had decreased significantly during the COVID-19 pandemic. The mean SER differences in myopic patients before COVID-19 compared with during the pandemic follow-up was -0.49 D (95% CI -0.53 to -0.45, p=0.00). So the prior pandemic myopic patients became more myopic during the pandemic follow-up time. CONCLUSION: During home quarantine, the mean SRE shifting in paediatrics accelerated. This phenomenon should be given more attention by policymakers, eyecare experts, educators and parents.

Necrosis of the optic nerve and chiasm with safe radiation doses: Report of two rare cases.

INTRODUCTION: Radiation-induced optic neuropathy (RION) is still a devastating complication of brain and skull base radiation that has no effective treatment up until today, thus uttermost caution must be taken in treating patients that brain radiotherapy is needed. We present two cases of RION that happened in seemingly safe radiation doses. CASE DESCRIPTION: A 48-year-old female with a history of pleomorphic pituitary adenoma developed bilateral and painless loss of vision 10 months after radiation to the brain; the total radiation dose was 45 Gy in 25 fractions and no other risk factors of RION were found. Magnetic resonance imaging of the brain depicted bilateral prechiasmatic optic nerve enhancement with involvement of the optic chiasm. Treatment with high doses of corticosteroids was unsuccessful. A 62-year-old female with a history of lung adenocarcinoma and brain metastases presented with a 1-month history of decreased vision in both eyes. He had undergone whole-brain radiotherapy with a total dose of 30 Gy over 10 fractions and concurrent chemotherapy with cisplatin and pemetrexed. Brain magnetic resonance imaging (MRI) with contrast showed bilateral intracranial optic nerve enhancement. CONCLUSIONS: This is the second case report of RION in a patient with a history of brain radiotherapy and concurrent chemotherapy with pemetrexed. History of chiasmal compression, concurrent use of chemotherapeutic agents, and high fraction size (despite the safety of total radiation dose) were possible contributing risk factors to develop RION in our cases. Hence, adjusting the radiation dose according to the presence of these risk factors is recommended.

Anterior and posterior ischemic optic neuropathy following liposuction surgery in a previously healthy young woman.

A previously healthy 28-year-old female developed bilateral painless vision loss, more prominent in the right eye than in the left, following abdominoplasty and liposuction surgery. Laboratory studies showed severe peri- and post-operative anemia. Over a 5-month follow-up, visual function remained decreased but stable in the right eye and improved in the left eye. This is the second reported case of anterior ischemic optic neuropathy in one eye and posterior ischemic optic neuropathy in the other eye after liposuction.Level of evidence: Level VI, case report study.