Primary Circumscribed Meningeal Melanoma Involving the Meckel's Cave: A Report of a Rare Case and Review of Literature.

Primary intracranial meningeal melanomas are rare. Diagnosing primary meningeal melanomas mostly involves comprehensive assessment through clinical and radiological means. This evaluation should encompass a detailed dermal and ophthalmic examination. Any suspicious lesion must be biopsied and examined microscopically. This is crucial not only to differentiate primary intracranial melanoma from other brain tumors but also to rule out metastases from potential sources of primary cutaneous or non-cutaneous melanomas. Surgery is considered the mainstay of treatment. Despite melanomas being generally considered radio- and chemo-resistant tumors, adjuvant radiotherapy and chemotherapy still play a crucial role in their management. The treatment landscape for primary meningeal melanoma is continually evolving, with ongoing research aiming to improve outcomes for patients with this challenging disease.

Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.

Mutations in the PCDH15 gene, encoding protocadherin-15, are among the leading causes of Usher syndrome type 1 (USH1F), and account for up to 12% USH1 cases worldwide. A founder truncating variant of PCDH15 has a ∼2% carrier frequency in Ashkenazi Jews accounting for nearly 60% of their USH1 cases. Although cochlear implants can restore hearing perception in USH1 patients, presently there are no effective treatments for the vision loss due to retinitis pigmentosa. We established a founder allele-specific Pcdh15 knockin mouse model as a platform to ascertain therapeutic strategies. Using a dual-vector approach to circumvent the size limitation of adeno-associated virus, we observed robust expression of exogenous PCDH15 in the retinae of Pcdh15KI mice, sustained recovery of electroretinogram amplitudes and key retinoid oxime, substantially improved light-dependent translocation of phototransduction proteins, and enhanced levels of retinal pigment epithelium-derived enzymes. Thus, our data raise hope and pave the way for future gene therapy trials in USH1F subjects.

Hypoxic oligodendrocyte precursor cell-derived VEGFA is associated with blood-brain barrier impairment.

Cerebral small vessel disease is characterised by decreased cerebral blood flow and blood-brain barrier impairments which play a key role in the development of white matter lesions. We hypothesised that cerebral hypoperfusion causes local hypoxia, affecting oligodendrocyte precursor cell-endothelial cell signalling leading to blood-brain barrier dysfunction as an early mechanism for the development of white matter lesions. Bilateral carotid artery stenosis was used as a mouse model for cerebral hypoperfusion. Pimonidazole, a hypoxic cell marker, was injected prior to humane sacrifice at day 7. Myelin content, vascular density, blood-brain barrier leakages, and hypoxic cell density were quantified. Primary mouse oligodendrocyte precursor cells were exposed to hypoxia and RNA sequencing was performed. Vegfa gene expression and protein secretion was examined in an oligodendrocyte precursor cell line exposed to hypoxia. Additionally, human blood plasma VEGFA levels were measured and correlated to blood-brain barrier permeability in normal-appearing white matter and white matter lesions of cerebral small vessel disease patients and controls. Cerebral blood flow was reduced in the stenosis mice, with an increase in hypoxic cell number and blood-brain barrier leakages in the cortical areas but no changes in myelin content or vascular density. Vegfa upregulation was identified in hypoxic oligodendrocyte precursor cells, which was mediated via Hif1α and Epas1. In humans, VEGFA plasma levels were increased in patients versus controls. VEGFA plasma levels were associated with increased blood-brain barrier permeability in normal appearing white matter of patients. Cerebral hypoperfusion mediates hypoxia induced VEGFA expression in oligodendrocyte precursor cells through Hif1α/Epas1 signalling. VEGFA could in turn increase BBB permeability. In humans, increased VEGFA plasma levels in cerebral small vessel disease patients were associated with increased blood-brain barrier permeability in the normal appearing white matter. Our results support a role of VEGFA expression in cerebral hypoperfusion as seen in cerebral small vessel disease.

Current Practice Of Histopathology In Pakistan: Difficulties, Challenges, And Solutions.

Histopathology is the gold standard for diagnosis of cancers as well as many non 14 neoplastic diseases. Pakistan is a country of more than 220 million people and the fifth most populated country of the world. Unfortunately, it has a weak healthcare system in general and poor pathology services in particular. Till date, only 338 histopathologists have passed their fellowship examination in Pakistan; this has led to a very alarming situation considering the marked increase in the prevalence of cancer cases and other diseases which need histopathological interpretation. There are only 18 big histopathological labs in the country, the majority of which are located in major cities which further delays the diagnosis of patients who live in rural areas. Immediate steps are required for better histopathology services in the country. Adoption of digital tools may bridge the gaps of histopathology-practice and ensure consistency across the country.

Novel Therapeutic Targets for Migraine.

Migraine, a primary headache disorder involving a dysfunctional trigeminal vascular system, remains a major debilitating neurological condition impacting many patients' quality of life. Despite the success of multiple new migraine therapies, not all patients achieve significant clinical benefits. The success of CGRP pathway-targeted therapy highlights the importance of translating the mechanistic understanding toward effective therapy. Ongoing research has identified multiple potential mechanisms in migraine signaling and nociception. In this narrative review, we discuss several potential emerging therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, δ-opioid receptor (DOR), potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels (ASIC). A better understanding of these mechanisms facilitates the discovery of novel therapeutic targets and provides more treatment options for improved clinical care.

Syntaxin 4 is essential for hearing in human and zebrafish.

Congenital hearing impairment (HI) is a genetically highly heterogeneous disorder in which prompt recognition and intervention are crucial to optimize outcomes. In this study, we used exome sequencing to investigate a large consanguineous Pakistani family with eight affected individuals showing bilateral severe-to-profound HI. This identified a homozygous splice region variant in STX4 (c.232 + 6T>C), which causes exon skipping and a frameshift, that segregated with HI (two-point logarithm of odds (LOD) score = 5.9). STX4, a member of the syntaxin family, is a component of the SNARE machinery involved in several vesicle transport and recycling pathways. In silico analysis showed that murine orthologue Stx4a is highly and widespread expressed in the developing and adult inner ear. Immunofluorescent imaging revealed localization of STX4A in the cell body, cell membrane and stereocilia of inner and outer hair cells. Furthermore, a morpholino-based knockdown of stx4 in zebrafish showed an abnormal startle response, morphological and developmental defects, and a disrupted mechanotransduction function in neuromast hair cells measured via FM1-43 uptake. Our findings indicate that STX4 dysfunction leads to HI in humans and zebrafish and supports the evolutionary conserved role of STX4 in inner ear development and hair cell functioning.

Single and binary adsorption of lead and cadmium ions in aqueous solutions and river water by butylamine functionalized vermiculite: performance and mechanism.

Lead and cadmium are toxic to human, animal, and plant health; they enhance oxidative stress indirectly while simultaneously acting through other toxicodynamic mechanisms. In this study, pristine vermiculite (VER) was functionalized with butylamine (BUT) and a novel organoclay (BUT-VER) adsorbent material was produced for simultaneous removal of Pb(II) and Cd(II) in aquatic medium. The adsorbents were characterized by spectroscopic, microscopic, spectrometric, and potentiometric techniques. The adsorption affecting parameters, including pH, time, initial concentration, temperature, and co-existing cations were investigated and optimized. The kinetic data results were in better agreement with pseudo-second-order (PSO) model (R2 > 0.992). Multiple isotherm models were used to study the adsorption system and results showed that adsorption was monolayer. The BUT-VER showed an improvement in adsorption capacity in a single system (Pb(II): from 134.2 to 160.6 mg g-1) and (Cd(II): from 51.1 to 58.9 mg g-1) while in binary system (Pb(II): from 107.3 to 114.5 mg g-1) and (Cd(II): from 33.7 to 39.7 mg g-1), respectively. Furthermore, BUT-VER was tested in real river water and removed efficiency of >99% was achieved in just 1 h. The dominant mechanisms were electrostatic attraction and complexation. BUT-VER was regenerated for five consecutive cycles and showed >90% removal efficiency. These findings suggest that the proposed inexpensive adsorbent has the potential for practical applications of toxic metals removal from water.

Photobiomodulation in Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Photobiomodulation (PBM) is a therapeutic modality that has gained increasing interest in neuroscience applications, including acute traumatic brain injury (TBI). Its proposed mechanisms for therapeutic effect when delivered to the injured brain include antiapoptotic and anti-inflammatory effects. This systematic review summarizes the available evidence for the value of PBM in improving outcomes in acute TBI and presents a meta-analysis of the pre-clinical evidence for neurological severity score (NSS) and lesion size in animal models of TBI. A systematic review of the literature was performed, with searches and data extraction performed independently in duplicate by two authors. Eighteen published articles were identified for inclusion: seventeen pre-clinical studies of in vivo animal models and one clinical study in human patients. The available human study supports safety and feasibility of PBM in acute moderate TBI. For pre-clinical studies, meta-analysis for NSS and lesion size were found to favor intervention versus control. Subgroup analysis based on PBM parameter variables for these outcomes was performed. Favorable parameters were identified as: wavelengths in the region of 665 nm and 810 nm; time to first administration of PBM ≤4 h; total number of daily treatments ≤3. No differences were identified between pulsed and continuous wave modes or energy delivery. Mechanistic substudies within included in vivo studies are presented and were found to support hypotheses of antiapoptotic, anti-inflammatory, and pro-proliferative effects, and a modulation of cellular metabolism. This systematic review provides substantial meta-analysis evidence of the benefits of PBM on functional and histological outcomes of TBI in in vivo mammalian models. Study design and PBM parameters should be closely considered for future human clinical studies.

Ingestion and impacts of water-borne polypropylene microplastics on Daphnia similis.

Polypropylene microplastics are the leading contaminant in aquatic environments, although research on their toxicity remains scarce. The proposed research focuses on the harmful consequences of acute exposure to polypropylene microplastics in Daphnia similis. This work converts widely available polypropylene bags into microplastics using xylene. FTIR findings demonstrated the lack of xylene residue in the produced polypropylene microplastic particles, which were spherical and ranged in size from 11.86 to 44.62 µm (FE-SEM). The results indicate that acute exposure to polypropylene microplastics causes immobility in D. similis. Ingestion of microplastics enhances the generation of reactive oxygen species (ROS), as shown by biochemical studies. Due to the production of free radicals in D. similis, the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) and a non-antioxidant enzyme of reduced glutathione (GSH) and also oxidative stress effects in lipid (lipid peroxidation - LPO), protein (carbonyl protein - CP) were increased. Additionally, the amount of the neurotransmitter enzyme acetylcholinesterase (AChE) activity was decreased. These findings indicate that the accumulation of polypropylene microplastics in the bodies of filter-feeding organisms should aggravate toxicity in the freshwater environment.

Does using 3D printed models for pre-operative planning improve surgical outcomes of foot and ankle fracture fixation? A systematic review and meta-analysis.

PURPOSE: The systematic review aims to establish the value of using 3D printing-assisted pre-operative planning, compared to conventional planning, for the operative management of foot and ankle fractures. METHODS: The systematic review was performed according to PRISMA guidelines. Two authors performed searches on three electronic databases. Studies were included if they conformed to pre-established eligibility criteria. Primary outcome measures included intraoperative blood loss, operation duration, and fluoroscopy time. The American orthopaedic foot and ankle score (AOFAS) was used as a secondary outcome. Quality assessment was completed using the Cochrane RoB2 form and a meta-analysis was performed to assess heterogeneity. RESULTS: Five studies met the inclusion and exclusion criteria and were eventually included in the review. A meta-analysis established that using 3D printed models for pre-operative planning resulted in a significant reduction in operation duration (mean difference [MD] = - 23.52 min, 95% CI [- 39.31, - 7.74], p = 0.003), intraoperative blood loss (MD = - 30.59 mL, 95% CI [- 46.31, - 14.87], p = 0.0001), and number of times fluoroscopy was used (MD = - 3.20 times, 95% CI [- 4.69, - 1.72], p < 0.0001). Using 3D printed models also significantly increased AOFAS score results (MD = 2.24, 95% CI [0.69, 3.78], p = 0.005), demonstrating improved ankle health. CONCLUSION: The systematic review provides promising evidence that 3D printing-assisted surgery significantly improves treatment for foot and ankle fractures in terms of operation duration, intraoperative blood loss, number of times fluoroscopy was used intraoperatively, and improved overall ankle health as measured by the AOFAS score.

Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury.

DNA double-strand breaks occur in many acute and long-term neurological conditions, including neurodegeneration, neurotrauma, and stroke. Nonrepaired breaks chronically activate the DNA damage response in neurons, leading to neural dysfunction and apoptosis. Here, we show that targeting of the central ATM-Chk2 pathway regulating the response to double-strand breaks slows neural decline in Drosophila models of chronic neurodegeneration. Inhibitors of ATM-Chk2, but not the parallel ATR-Chk1 pathway, also promote marked, functional recovery after acute central nervous system injury in rats, suggesting that inhibiting nonhomologous end-joining rather than homologous recombination is crucial for neuroprotection. We demonstrate that the Chk2 inhibitor, prexasertib, which has been evaluated in phase 2 clinical trials for cancer, has potent neuroprotective effects and represents a new treatment option to promote functional recovery after spinal cord or optic nerve injury.

Long-Term Anatomic and Visual Outcomes of Planned Preterm Delivery and Treatment of Norrie Disease.

We previously reported that planned preterm delivery at 34 weeks gestational age provided an opportunity to treat Norrie disease in the vasoproliferative phase, prevented infantile retinal detachment, and preserved functional vision without further treatment after infancy. Although retinal vascularization did not proceed postnatally, after 8 years of follow-up, the retinas remained attached, and rudimentary foveal development was observed by optical coherence tomography. Best corrected visual acuity gradually improved to 20/80 with both eyes, and visual fields and real-world visual performance were remarkably functional. Global development progressed appropriately, and no long-term sequelae of premature delivery were observed. [Ophthalmic Surg Lasers Imaging Retina 2022;53:464-467.].

Regulatory mechanism of montmorillonite on antibiotic resistance genes in Escherichia coli induced by cadmium.

The emergence and spread of antibiotic resistance genes (ARGs) induced by the overuse of antibiotics has become a serious threat to public health. Heavy metals will bring longer-term selection pressure to ARGs when the concentration of their residues is higher than that of antibiotics in environmental media. To explore the potential roles of montmorillonite (Mt) in the emergence of ARGs under divalent cadmium ion (Cd2+) stress, Escherichia coli (E. coli) was induced continuously for 15 days under Cd2+ gradient concentrations (16, 32, 64, 96, and 128 µg∙mL-1) with and without Mt. Subsequently, antibiotic resistance testing, transcriptomics, transmission electron microscope, scanning electron microscopy, and Fourier transform infrared were conducted for analysis. The results of characterization analysis showed that Cd2+could enhance the expression of resistance genes such as penicillin, tetracycline, macrolactone, and chloramphenicol in E. coli. Moreover, compared with Cd2+, Mt-Cd could inhibit the promotion of these resistances by alleviating the expressions of genes involved in cell wall/membrane, protein synthesis, transport systems, signal transduction, and energy supply processes. Therefore, the study promoted the understanding of Cd2+ in triggering bacterial antibiotic resistance and highlighted a novel theme of clay's ability to mitigate ecological risk of antibiotic resistance caused by heavy metals. KEY POINTS: • Montmorillonite (Mt) could inhibit the promotion of antibiotic resistances. • E. coli formed a unique resistance mechanism by interacting with Mt and Cd2+. • Mt stimulated cellular signal transduction, cellular component, and energy supply.

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein.

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can "block" P-gp-mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.

Protocadherin 15 suppresses oligodendrocyte progenitor cell proliferation and promotes motility through distinct signalling pathways.

Oligodendrocyte progenitor cells (OPCs) express protocadherin 15 (Pcdh15), a member of the cadherin superfamily of transmembrane proteins. Little is known about the function of Pcdh15 in the central nervous system (CNS), however, Pcdh15 expression can predict glioma aggression and promote the separation of embryonic human OPCs immediately following a cell division. Herein, we show that Pcdh15 knockdown significantly increases extracellular signal-related kinase (ERK) phosphorylation and activation to enhance OPC proliferation in vitro. Furthermore, Pcdh15 knockdown elevates Cdc42-Arp2/3 signalling and impairs actin kinetics, reducing the frequency of lamellipodial extrusion and slowing filopodial withdrawal. Pcdh15 knockdown also reduces the number of processes supported by each OPC and new process generation. Our data indicate that Pcdh15 is a critical regulator of OPC proliferation and process motility, behaviours that characterise the function of these cells in the healthy CNS, and provide mechanistic insight into the role that Pcdh15 might play in glioma progression.

Use of Computed Tomography Coronary Calcium Score for Coronary Artery Disease Risk Stratification During Liver Transplant Evaluation.

Background: End-stage liver disease (ESLD) is not considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, lifestyle characteristics commonly associated with increased ASCVD risk are highly prevalent in ESLD. Emerging literature shows a high burden of asymptomatic coronary artery disease (CAD) in patients with ESLD and a high ASCVD risk in liver transplantation (LT) recipients. Coronary artery calcium score (CAC) is a noninvasive test providing reliable CAD risk stratification. We implemented an LT evaluation protocol with CAC playing a central role in triaging and determining the need for further CAD assessment. Here, we inform our results from this early experience. Methods: Patients with ESLD referred for LT evaluation were prospectively studied. We compared accuracy of CAC against that of CAD risk factors/scores, troponin I, dobutamine stress echocardiogram (DSE), and single-photon emission computed tomography (SPECT) to detect coronary stenosis ≥70 (CAD ≥ 70) per left heart catheterization (LHC). Thirty-day post-LT cardiac outcomes were also analyzed. Results: One hundred twenty-four of 148 (84%) patients underwent CAC, 106 (72%) DSE/SPECT, and 50 (34%) LHC. CAC ≥ 400 was found in 35 (28%), 100 to 399 in 17 (14%), and <100 in 72 (58%). LHC identified CAD ≥ 70% in 8 of 29 (28%), 2 of 9 (22%), and 0 of 4, respectively. Two acute coronary syndromes occurred after LT in a patient with CAC 811 (CAD < 70%), and one with CAC 347 (CAD ≥ 70%). No patients with CAC < 100 presented with acute coronary syndrome after LT. When using CAD ≥ 70% as primary endpoint of LT evaluation, CAC ≥ 346 was the only test showing predictive usefulness (negative predictive value 100%). Conclusions: CAC is a promising tool to guide CAD risk stratification and need for LHC during LT evaluation. Patients with a CAC < 100 can safely undergo LT without the need for LHC or cardiac stress testing, whereas a CAC < 346 accurately rules out significant CAD stenosis (≥70%) on LHC, outperforming other CAD risk-stratification strategies.

Identification of Frameshift Variants in POLH Gene Causing Xeroderma Pigmentosum in Two Consanguineous Pakistani Families.

Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder characterized by severe sensitivity of skin to sunlight and an increased risk of skin cancer. XP variant (XPV), a milder subtype, is caused by variants in the POLH gene. POLH encodes an error-prone DNA-polymerase eta (pol eta) which performs translesion synthesis past ultraviolet photoproducts. The current study documents the clinical and genetic investigations of two large consanguineous Pakistani families affected with XPV. In family 1, whole exome sequencing (WES) revealed a novel frameshift variant, c.1723dupG (p.(Val575Glyfs*4)), of POLH, which is predicted to cause frameshift and premature truncation of the encoded enzyme. Indeed, our ex vivo studies in HEK293T cells confirmed the truncation of the encoded protein due to the c.1723dupG variant. In family 2, Sanger sequencing of POLH exons, revealed a recurrent nonsense variant, c.437dupA (p.Tyr146*). POLH forms a hetero-tetrameric POLZ complex with REV3L, REV7, POLD2 and POLD3. Next, we performed in silico analysis of POLH and other POLZ complex genes expression in publicly available single cell mRNAseq datasets from adult human healthy and aging skin. We found overlapping expression of POLH, REV3L and POLD2 in multiple cell types including differentiated and undifferentiated keratinocytes, pericytes and melanocytes in healthy skin. However, in aging human skin, POLH expression is reduced in compare to its POLZ complex partners. Insights from our study will facilitate counseling regarding the molecular and phenotypic landscape of POLH-related XPV.

A Comprehensive Review of Management of Colorectal Liver Mets in the Current Era.

Colorectal carcinoma is the third most common cancer in the US. The liver tends to be the most common site of metastasis. This review provides an in-depth analysis of non-transplant options available in the management of colorectal liver mets.

Association between Preoperative Steroids and Outcomes in Patients Undergoing Pancreaticoduodenectomy using the National Surgical Quality Improvement Program.

BACKGROUND: A national study analyzing the association between preoperative steroid use and outcomes after pancreatic resections is lacking. The purpose of this study is to evaluate the association between preoperative steroids and outcomes after pancreaticoduodenectomy using a national database. MATERIALS AND METHODS: A retrospective analysis of patients undergoing pancreaticoduodenectomy was performed using the National Surgical Quality Improvement Program (NSQIP) database (2014-2019). In addition, we utilized propensity score matching to compare patients on preoperative steroids to those who were not. Outcomes measured included 30-day complications and mortality, need for readmission, a prolonged hospital length of stay, delayed gastric emptying, and pancreatic fistula. RESULTS: After propensity score matching, there were 438 patients in the steroid group and 876 patients in the no steroid group. There was no difference in pancreatic fistula (23.8% vs. 21.7%; p-0.3), delayed gastric emptying (21.1% vs.20.1%; p-0.06), major complications (31.8% vs. 30.1%; p-0.1), and mortality (3.5% vs. 3.2%; p-0.6) between the two groups. CONCLUSION: Glucocorticoids did not reduce the incidence of overall complications, postoperative fistula, and delayed gastric emptying following pancreaticoduodenectomy.

Corneal Structural Changes in Congenital Glaucoma.

OBJECTIVE: To identify corneal structure differences on quantitative high-frequency ultrasound biomicroscopy (UBM) among subjects with congenital glaucoma compared with controls. METHODS: This prospective case-control study evaluated 180 UBM images from 44 eyes of 30 subjects (18 control and 12 glaucoma, mean age 5.2±8.0 years, range 0.2-25.8 years) enrolled in the Pediatric Anterior Segment Imaging and Innovation Study (PASIIS). ImageJ was used to quantify a comprehensive set of corneal structures according to 21 quantitative parameters. Statistical analysis compared corneal measurements in glaucoma subtypes and age-matched controls with significance testing and mixed effects models. RESULTS: Significant differences between congenital glaucoma cases and controls were identified in 16 of 21 measured parameters including angle-to-angle, central and peripheral corneal thicknesses, scleral integrated pixel density, anterior corneal radius of curvature, and posterior corneal radius of curvature. Eight parameters differed significantly between primary congenital glaucoma and glaucoma following congenital cataract surgery. CONCLUSION: Multiple measurable corneal structural differences exist between congenital glaucoma and control eyes, and between primary and secondary congenital glaucoma, including but not limited to corneal width and thickness. The structural differences can be quantified from UBM image analysis. Further studies are needed to determine whether corneal features associated with glaucoma can be used to diagnose or monitor progression of congenital glaucoma.