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Objective Animals Studied Procedures Results Conclusions To evaluate the effects of latanoprostene bunod on intraocular pressure (IOP) and pupil diameter (PD) in normal cats and cats with feline congenital glaucoma (FCG).Five normal and 5 FCG cats.This masked, controlled crossover study comprised a 1‐day Pre‐treatment phase followed by two 10‐day Treatment phases, each followed by a 10‐day Recovery phase. During treatment, all cats received twice daily 0.005% latanoprost (LAT) or 0.024% latanoprostene bunod (LBN) in a randomized eye. Following Recovery, the same eye was treated with the opposite drug. Contralateral eyes served as saline‐treated controls. Intraocular pressure and PD measurements were performed three times daily during all study phases. Data were analyzed via constrained longitudinal data analysis models.Neither drug significantly reduced IOP in normal cats. In FCG cats, statistically significant reductions in mean (95% CI) IOP were observed relative to controls 4 h after LAT and LBN treatment (−5.5 mmHg [−8.4, −2.5], p < .001, −7.2 mmHg [−10.2, −4.3], p < .001, respectively). These differences represented 28.4% and 37.9% IOP reductions, respectively. Mean IOP reduction after 4 h was significantly greater with LBN treatment compared to LAT (−1.8 mmHg [−3.2, −0.4], p = .012). However, these IOP reductions were not considered clinically significant. Both drugs similarly reduced PD in normal and FCG cats.Transient IOP reduction was observed after topical administration of LAT and LBN in FCG cats; and mean IOP difference was statistically significantly greater in LBN‐treated eyes. However, the apparent enhanced hypotensive effect of LBN is not clinically significant. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Not only germline but also postzygotic mutations in the RASA1 or EPHB4 genes can lead to capillary malformation‐arteriovenous malformation (CM‐AVM) syndrome. As it is not always possible to clinically distinguish between constitutional variants and postzygotic mosaicism, a sufficiently high sequencing depth must be used in genetic diagnostics to detect both. Capillary malformation‐arteriovenous malformation (CM‐AVM) syndrome, with or without Parkes Weber syndrome, is a rare autosomal dominant disease caused by pathogenic RASA1 or EPHB4 variants. Up to 80% of CM‐AVM cases have an affected parent. Gene panel sequencing was performed for a 4‐year‐old girl with multiple CMs, two capillary stains on the left leg, and associated overgrowth of the second toe. We also reviewed published cases with mosaic RASA1 and EPHB4 mutations. A mosaic RASA1 loss‐of‐function mutation was detected with a variant allele frequency (VAF) of 20% in the blood and oral epithelial cells of the index patient. The literature review illustrates that the severity of the clinical phenotype does not correlate with the VAF. We also identified a germline nonsense variant in the patient's TEK gene. However, inactivating TEK variants do not cause a vascular phenotype but can confer an increased risk for primary congenital glaucoma with variable expressivity. The case presented here illustrates that the choice of the sequencing depth of a diagnostic next‐generation sequencing test for CM‐AVM patients should always take mosaicism into account and that a good knowledge of the sequenced genes and associated disease mechanisms is necessary for adequate genetic counseling. [ABSTRACT FROM AUTHOR]

Childhood glaucoma is a heterogeneous group of ocular disorders defined by an age of onset from birth to 18 years. These vision‐threatening disorders require early diagnosis, timely treatment, and lifelong management to maintain vision and minimise irreversible blindness. The genetics of childhood glaucoma is complex with both phenotypic and genetic heterogeneity. The purpose of this review is to summarise the different types of childhood glaucoma and their genetic architecture to aid in the genetic counselling process with patients and their families. We provide an overview of associated syndromes and discuss implications for genetic counselling, including genetic testing strategies, cascade genetic testing, and reproductive options. [ABSTRACT FROM AUTHOR]

Superoxide Dismutase 3 (SOD3) scavenges extracellular superoxide giving a hydrogen peroxide metabolite. Both Reactive Oxygen Species diffuse through aquaporins causing oxidative stress and biomolecular damage. SOD3 is differentially expressed in cancer and this research utilises Gene Expression Omnibus data series GSE2109 with 2,158 cancer samples. Genome-wide expression correlation analysis was conducted with SOD3 as the seed gene. Categorical SOD3 Pearson Correlation gene lists incrementing in correlation strength by 0.01 from ρ≥|0.34| to ρ≥|0.41| were extracted from the data. Positively and negatively SOD3 correlated genes were separated for each list and checked for significance against disease overlapping genes in the ClinVar and Orphanet databases via Enrichr. Disease causal genes were added to the relevant gene list and checked against Gene Ontology, Phenotype Ontology, and Elsevier Pathways via Enrichr before the significant ontologies containing causal and non-overlapping genes were reviewed with a literature search for possible disease and oxidative stress associations. 12 significant individually discriminated disorders were identified: Autosomal Dominant Cutis Laxa (p = 6.05x10-7), Renal Tubular Dysgenesis of Genetic Origin (p = 6.05x10-7), Lethal Arteriopathy Syndrome due to Fibulin-4 Deficiency (p = 6.54x10-9), EMILIN-1-related Connective Tissue Disease (p = 6.54x10-9), Holt-Oram Syndrome (p = 7.72x10-10), Multisystemic Smooth Muscle Dysfunction Syndrome (p = 9.95x10-15), Distal Hereditary Motor Neuropathy type 2 (p = 4.48x10-7), Congenital Glaucoma (p = 5.24x210-9), Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (p = 3.77x10-16), Classical-like Ehlers-Danlos Syndrome type 1 (p = 3.77x10-16), Retinoblastoma (p = 1.9x10-8), and Lynch Syndrome (p = 5.04x10-9). 35 novel (21 unique) genes across 12 disorders were identified: ADNP, AOC3, CDC42EP2, CHTOP, CNN1, DES, FOXF1, FXR1, HLTF, KCNMB1, MTF2, MYH11, PLN, PNPLA2, REST, SGCA, SORBS1, SYNPO2, TAGLN, WAPL, and ZMYM4. These genes are proffered as potential biomarkers or therapeutic targets for the corresponding rare diseases discussed. [ABSTRACT FROM AUTHOR]

PurposeCase reportConclusionTo report the occurrence of unilateral, neonatal-onset congenital glaucoma in a child with Rubinstein–Taybi Syndrome (RTS).A 15-day-old male with features of RTS was presented with an enlarged corneal diameter, corneal haze, and peripheral corneal vascularization of the left eye. Ultrasound biomicroscopy of his left eye revealed iris atrophy, iridocorneal adhesions, and iris adhesions to a partially absorbed cataractous lens. Genetic evaluation of the child and the parents revealed a novel de novo heterozygous pathogenic variant in exon 5 of the CREBBP gene (NM_004380.3:c.1390C>T). A diode laser cyclophotocoagulation was performed to control the IOP in the left eye.Unilateral neonatal-onset congenital glaucoma due to iridocorneal adhesions can be a rare presentation of Rubinstein–Taybi Syndrome. [ABSTRACT FROM AUTHOR]

Objectives: To determine the efficacy of modified combined trabeculotomy-trabeculectomy (CTT) with mitomycin-C (MMC) versus conventional CTT with MMC for intraocular pressure (IOP) reduction in patients with primary congenital glaucoma (PCG). Methods: This interventional study was carried out in The Institute of Ophthalmology, Lahore from January 2018 to June 2019. We included 70 patients of either gender, with the age range from birth to ten years and with PCG having IOP >30 mm Hg. These patients were divided in groups A and B with 35 patients in each group. Patients in Group-A underwent modified CTT with MMC and in Group-B conventional CTT with MMC was carried out. Results: The mean age of our patients was 15.17 ± 12.39 months. Regarding gender, 57 (81.4%) were males and 13 (18.6%) were females. Baseline mean IOP in Group-A was 32.49 ± 1.01 mm Hg whereas in Group-B mean IOP was 31.97 ± 1.04 mm Hg. After one month, the mean IOP was 27.60 ± 1.72 mm Hg in Group-A, whereas mean IOP was 27.40 ± 1.82 mmHg in Group-B. After three months, the mean IOP was 21.63 ± 1.09 mm Hg in Group-A, whereas 20.97 ± 1.12 mm Hg in Group-B. In Group-A efficacy was achieved in 14 (40%) patients whereas in Group-B efficacy was achieved in 25 (71.4%) patients. Conclusion: Our study revealed that conventional CTT with MMC showed better efficacy than modified CTT with MMC for reduction of IOP in PCG. [ABSTRACT FROM AUTHOR]

Abstract Background Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that commonly involves skin, nerves, and skeletal system with increased neoplastic predisposition. This disease has been rarely associated with multiple congenital anomalies. Herein, we describe an Egyptian child with NF1 and coexistent bilateral congenital glaucoma, giant congenital melanocytic nevi (GCMN), alopecia, and hypospadias. Case presentation A 2.5-year-old boy presented with developmental delay, back swelling, and multiple congenital anomalies. His father and two sisters were known to have NF1. The child was diagnosed with bilateral primary congenital glaucoma at the age of 3.5 months and underwent trabeculectomy with mitomycin C therapy. Examination at the age of 5 months revealed marked hypotonia, multiple GCMN, scanty café-au-lait macules, left upper eyelid plexiform neuroma and trichomegaly, hypertrichosis of left eyebrow, hypertelorism, depressed nasal bridge, left frontal scalp alopecia, and distal penile hypospadias. At the age of 8 months, brain imaging depicted a markedly dilated left lateral ventricle, and he underwent ventriculoperitoneal shunt surgery. The child developed back swelling at the age of 2.5 years, and a spinal magnetic resonance image showed bilateral multiple spinal neurofibromas in the paraspinal region with intraspinal extensions. A whole exome sequencing identified a heterozygous missense variant NM_001042492.3:c.1466A > G (NP_001035957.1:p.Tyr489Cys) in NF1 gene. Conclusions The present case report adds to the knowledge of the phenotypic spectrum and variability of NF1 by reporting the association of multiple unusual congenital anomalies. Importantly, such congenital anomalies could be the first presenting features in patients with NF1 since cafe´-au-lait macules and other typical diagnostic criteria may not be apparent in the neonatal period and early infancy. Accordingly, NF1 should be considered in newborns with congenital glaucoma, GCMN, scalp alopecia, and hypospadias.

Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that commonly involves skin, nerves, and skeletal system with increased neoplastic predisposition. This disease has been rarely associated with multiple congenital anomalies. Herein, we describe an Egyptian child with NF1 and coexistent bilateral congenital glaucoma, giant congenital melanocytic nevi (GCMN), alopecia, and hypospadias. Case presentation: A 2.5-year-old boy presented with developmental delay, back swelling, and multiple congenital anomalies. His father and two sisters were known to have NF1. The child was diagnosed with bilateral primary congenital glaucoma at the age of 3.5 months and underwent trabeculectomy with mitomycin C therapy. Examination at the age of 5 months revealed marked hypotonia, multiple GCMN, scanty café-au-lait macules, left upper eyelid plexiform neuroma and trichomegaly, hypertrichosis of left eyebrow, hypertelorism, depressed nasal bridge, left frontal scalp alopecia, and distal penile hypospadias. At the age of 8 months, brain imaging depicted a markedly dilated left lateral ventricle, and he underwent ventriculoperitoneal shunt surgery. The child developed back swelling at the age of 2.5 years, and a spinal magnetic resonance image showed bilateral multiple spinal neurofibromas in the paraspinal region with intraspinal extensions. A whole exome sequencing identified a heterozygous missense variant NM_001042492.3:c.1466A > G (NP_001035957.1:p.Tyr489Cys) in NF1 gene. Conclusions: The present case report adds to the knowledge of the phenotypic spectrum and variability of NF1 by reporting the association of multiple unusual congenital anomalies. Importantly, such congenital anomalies could be the first presenting features in patients with NF1 since cafe´-au-lait macules and other typical diagnostic criteria may not be apparent in the neonatal period and early infancy. Accordingly, NF1 should be considered in newborns with congenital glaucoma, GCMN, scalp alopecia, and hypospadias. [ABSTRACT FROM AUTHOR]

Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in CYP1B1, LTBP2, and TEK and their interactions with MYOC, FOXC1, and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes (MYOC) and perform ciliary functions (TEK), we explored the involvement of a core centrosomal protein, CEP164, which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E, which synergistically interacts with CEP164, and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and efficacy of the PAUL Glaucoma Implant (PGI) for managing refractory primary congenital glaucoma (PCG) over a one-year period. Study Design: Retrospective. Methods: A study was conducted using the medical records of thirty eyes of 17 patients who underwent PGI surgery for the treatment of refractory PCG. Primary outcome measures included failure criteria such as intraocular pressure (IOP) > 21 mm Hg, < 20% IOP reduction, necessity for further glaucoma intervention, implant removal, or loss of vision. Secondary outcomes focused on mean IOP, average number of glaucoma medications, best corrected visual acuity (logMAR), and incidence of complications. Results: The mean preoperative IOP of 38.8 ± 9.2 mmHg significantly decreased to 16.1 ± 3.3 mmHg at 12 months postoperatively (p < 0.001). The average number of glaucoma medications reduced from 3.6 ± 0.5 preoperatively to 0.9 ± 1.2 at 12 months post-op. Visual acuity remained stable in 24 eyes, decreased in 4, and increased in 2. Early postoperative complications occurred in 13.3% of patients, but no late complications were reported. The cumulative success rate was 86.6%. Conclusion: The PGI appears to be a safe and effective option for managing refractory primary congenital glaucoma, demonstrating significant IOP reduction and decreased dependence on glaucoma medications over a one-year period, with a high success rate and manageable complication profile. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Treatment with glucocorticoids following paediatric cataract surgery is crucial to prevent inflammation, but may lead to secondary glaucoma, and hypothalamic–pituitary–adrenal axis suppression. We wish to compare glaucoma outcomes following high‐dose and low‐dose glucocorticoid treatment after paediatric cataract surgery.This cohort study included Danish children undergoing cataract surgery before 10 years of age, receiving either a low‐dose or high‐dose postoperative glucocorticoid treatment. Case identification and collection of a standardized dataset were retrospective, from 1 January 2010 to 31 December 2016, and prospective thereafter, until 31 December 2021. High‐dose treatment included 0.5–1.0 mg subconjunctival depot dexamethasone or methylprednisolone, followed by 6–8 drops of dexamethasone for 1 week, tapered by one drop weekly. Low‐dose treatment included 6 drops for 3 days, followed by 3 drops for 18 days. Sustained (>3 months) ocular hypertension or glaucoma was compared between the two groups.Overall, 267 children (388 eyes) were included in the study. Ninety‐five children (133 eyes) had received high‐dose treatment and had a median follow‐up time of 89 months (IQR: 57.2–107.4), while 173 children (255 eyes) had received the low‐dose treatment and had a median follow‐up time of 40.5 months (IQR: 22.9–60.4). Survival curves showed a lower risk of glaucoma in the low‐dose group for children with axial lengths ≥18 mm.Low‐dose glucocorticoid treatment was associated with a lower risk of glaucoma in children with axial lengths ≥18 mm. The same effect was not observed in children with shorter eyes. High‐dose glucocorticoid should be limited in children undergoing cataract surgery. [ABSTRACT FROM AUTHOR]

Objective: To describe the inheritance pattern and clinical variability of primary congenital glaucoma (PCG) in a family with two affected siblings. Materials and Methods: Two sisters diagnosed at birth with bilateral PCG, whose father had bilateral PCG and mother had bilateral microphthalmus, were subjected to a familial genetic study and ophthalmologic follow-up including intraocular pressure (IOP) measurement, and collection of biometric and cup-to-disc ratio data. Results: The inheritance pattern was autosomal recessive in compound heterozygosis. The sisters were found to be carriers of three pathogenic allele variants of the CYP1B1 gene: c.317C>A (p.Ala106Asp) and c.1345delG (p.Asp449MetfsTer8) in one patient (10 years) and c.1345delG (p.Asp449MetfsTer8) and c.202_209delCAGGCGGC (p.Gln68Serfs153Ter) in her older sister (12 years). Surgical histories included: three goniotomies and two Ahmed valves in each eye, and two trabeculectomies and a pupilloplasty in the right eye in the 10-year old; and one goniotomy, trabeculectomy and three Ahmed valves in each eye in the older sister. Currently, both sisters have a controlled intraocular pressure of 18–20 mmHg in both eyes. The father is blind in both eyes and carries two variants c.317C>A (p.Ala106Asp) and c.202_209delCAGGCGGC (p.Gln68Serfs153Ter). The mother with a single variant c.1345delG (p.Asp440MetfsTer8) has a prosthetic right eye and microphthalmus left eye. Conclusions: The sisters were found to show two different allelic CYP1B1 variants (compound heterozygosis) with different repercussions on the clinical severity of PCG. These findings highlight the importance of genetic screening of affected families. [ABSTRACT FROM AUTHOR]

Purpose: This study assesses the effectiveness and safety of using Ologen implants (Aeon Astron Europe BV, Leiden, The Netherlands) as an adjunctive therapy in childhood glaucoma surgeries. Methods: We systematically reviewed the existing literature across various electronic databases to examine the effectiveness and safety of Ologen implants in childhood glaucoma surgeries. Results: Our analysis encompassed 14 studies on the use of Ologen implants in childhood glaucoma. Among these, seven were prospective, five were retrospective, and two did not specify their study design. Success rates varied depending on the type of surgery and the included childhood glaucoma subtype. The success rates for Ologen implants-augmented surgeries were as follows: 33.3-70% for trabeculectomy, 50-81% for combined trabeculotomy-trabeculectomy procedure, 33%-87% for glaucoma drainage device, and 60% in deep sclerectomy. Conclusion: Ologen implant has a potential role in mitigating postoperative fibrosis and enhancing success rates in various childhood glaucoma surgeries. However, the existing literature is limited. Future comparative prospective studies with larger cohorts are needed. [ABSTRACT FROM AUTHOR]

Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants. Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997–2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI. Results: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2). Conclusion: Variation in the genes identified in this population‐based study may help to further explain the genetics of PCG. [ABSTRACT FROM AUTHOR]

Sturge–Weber syndrome (SWS), also known as encephalo-trigeminal angiomatosis, is a sporadic, congenital neurocutaneous disorder. It is characterized by capillary malformation affecting the brain, meninges, eyes, and skin. The ophthalmic, maxillary, and mandibular distributions of the trigeminal nerve are involved. Eye involvement with vascular malformation produces glaucoma and can lead to vision loss. Here, we present a rare case of SWS with port-wine stain, painful vision loss in left eye, and open-angle glaucoma in the other eye of the same patient. The painful blind eye was treated with cyclocryotherapy with successful control of intraocular pressure.

Mawaddah Sabr,1,&ast; Valmore A Semidey,2 Marcos J Rubio-Caso,2 Renad Aljuhani Jnr,3 Gorka Sesma1,&ast; 1Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 3Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Gorka Sesma, Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Al Urubah Branche Road, West Building 2nd Floor, Riyadh, 11462, Saudi Arabia, Tel +966114849700, Fax +966114821908, Email gsesma@kkesh.med.saBackground: Retinal detachment is a major postsurgical threat in pediatric cataract surgery; however, the effect of axial length remains unclear. This study aimed to assess the relationship between axial length and detachment risk in vulnerable patients.Methods: This retrospective cohort study analyzed 132 eyes of 84 pediatric cataract surgery patients aged < 20 years old. Axial length was measured preoperatively, and the incidence of retinal detachment was recorded over a median follow-up of 4 years. Logistic regression analysis was used to examine the axial length-detachment relationship.Results: Twenty eyes had postoperative retinal detachments. The median axial length was longer in the detachment group (23.6 mm) than in the non-detachment group (21.6 mm). Eyes with axial length ≤ 23.4 mm had 0.55-fold decreased odds of detachment compared to longer eyes. Preexisting myopia and glaucoma confer heightened risk. Approximately half of the patients retained some detachment risk eight years postoperatively.Conclusion: Shorter eyes (axial length ≤ 23.4 mm) appear to be protected against pediatric retinal detachment after cataract surgery, whereas myopia, glaucoma, and axial elongation > 23.4 mm elevate the postoperative risk. Understanding these anatomical risk profiles requires surgical planning and follow-up care of children undergoing lensectomy.Plain language Summary: This study investigated the protective role of a shorter axial length in preventing retinal detachment after pediatric cataract surgery. This highlights the correlation between smaller eye sizes and reduced detachment risk, emphasizing the need for careful consideration of anatomical factors in surgical planning and patient monitoring, particularly for patients with preexisting myopia or postoperative glaucoma. Keywords: pediatric cataract surgery, axial length, retinal detachment, myopia, congenital glaucoma, congenital cataract

Abstract Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% of childhood blindness worldwide. Understanding the molecular aetiology is key to improving diagnosis, prognosis and unlocking the potential for optimising clinical management. In this study, we investigated 86 CG cases from 78 unrelated families of diverse ethnic backgrounds, recruited into the Genomics England 100,000 Genomes Project (GE100KGP) rare disease cohort, to improve the genetic diagnostic yield. Using the Genomics England/Genomic Medicine Centres (GE/GMC) diagnostic pipeline, 13 unrelated families were solved (13/78, 17%). Further interrogation using an expanded gene panel yielded a molecular diagnosis in 7 more unrelated families (7/78, 9%). This analysis effectively raises the total number of solved CG families in the GE100KGP to 26% (20/78 families). Twenty-five percent (5/20) of the solved families had primary congenital glaucoma (PCG), while 75% (15/20) had secondary CG; 53% of this group had non-acquired ocular anomalies (including iris hypoplasia, megalocornea, ectopia pupillae, retinal dystrophy, and refractive errors) and 47% had non-acquired systemic diseases such as cardiac abnormalities, hearing impairment, and developmental delay. CYP1B1 was the most frequently implicated gene, accounting for 55% (11/20) of the solved families. We identified two novel likely pathogenic variants in the TEK gene, in addition to one novel pathogenic copy number variant (CNV) in FOXC1. Variants that passed undetected in the GE100KGP diagnostic pipeline were likely due to limitations of the tiering process, the use of smaller gene panels during analysis, and the prioritisation of coding SNVs and indels over larger structural variants, CNVs, and non-coding variants.

Objective: To investigate the relationship between corneal diameter and internal corneal span determined from angle-to-angle distance using ultrasound biomicroscopy (UBM) in an observational cross-sectional patient population comprised of 54 eyes (28 healthy control eyes, ages 0.1 to 11.3 years; 26 eyes with primary congenital glaucoma, ages 0.1 to 3.5 years) from 41 pediatric participants ages 0.1 to 11.3 years (mean age: 3±3 years, median age: 2 years). Methods: Forty cornea photographs with reference ruler and 110 UBM images were obtained. Three observers measured horizontal and vertical corneal diameter and angle-to-angle distance in each cornea photo and UBM image using ImageJ and the average values were used. Main outcome measures were Pearson correlation coefficient, linear regression, mean difference between corneal diameter and angle-to-angle distance, and intra-class correlation coefficients among measurements from all three observers for each parameter. Results: Corneal diameter and angle-to-angle distance had a strong positive correlation horizontally (Pearson r = 0.89, p<0.001) and vertically (r = 0.93, p<0.001). Correlation was consistent regardless of presence of primary congenital glaucoma and participant age. Regression analysis demonstrated a linear relationship between the parameters for horizontal (CD = 0.99*AA+0.28, R2 = 0.81, p<0.001) and vertical (CD = 0.91 *AA+1.32, R2 = 0.85, p<0.001) dimensions. Overall, reliability was good-excellent, ranging from an ICC of 0.76 for vertical corneal diameter to 0.90 for horizontal angle-to-angle distance. Conclusions: Based on the strong positive correlation found between corneal diameter and angle-to-angle distance in our study population, UBM image analysis can be used to accurately estimate corneal diameter from angle-to-angle distance in children with healthy eyes and primary congenital glaucoma. UBM may provide a useful intraocular alternative for estimating corneal diameter and monitoring diseases that affect the cornea in infants and children, such as congenital glaucoma. [ABSTRACT FROM AUTHOR]

Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% of childhood blindness worldwide. Understanding the molecular aetiology is key to improving diagnosis, prognosis and unlocking the potential for optimising clinical management. In this study, we investigated 86 CG cases from 78 unrelated families of diverse ethnic backgrounds, recruited into the Genomics England 100,000 Genomes Project (GE100KGP) rare disease cohort, to improve the genetic diagnostic yield. Using the Genomics England/Genomic Medicine Centres (GE/GMC) diagnostic pipeline, 13 unrelated families were solved (13/78, 17%). Further interrogation using an expanded gene panel yielded a molecular diagnosis in 7 more unrelated families (7/78, 9%). This analysis effectively raises the total number of solved CG families in the GE100KGP to 26% (20/78 families). Twenty-five percent (5/20) of the solved families had primary congenital glaucoma (PCG), while 75% (15/20) had secondary CG; 53% of this group had non-acquired ocular anomalies (including iris hypoplasia, megalocornea, ectopia pupillae, retinal dystrophy, and refractive errors) and 47% had non-acquired systemic diseases such as cardiac abnormalities, hearing impairment, and developmental delay. CYP1B1 was the most frequently implicated gene, accounting for 55% (11/20) of the solved families. We identified two novel likely pathogenic variants in the TEK gene, in addition to one novel pathogenic copy number variant (CNV) in FOXC1. Variants that passed undetected in the GE100KGP diagnostic pipeline were likely due to limitations of the tiering process, the use of smaller gene panels during analysis, and the prioritisation of coding SNVs and indels over larger structural variants, CNVs, and non-coding variants. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the short-term efficacy and safety of the Paul Glaucoma Implant (PGI) in pediatric eyes diagnosed with glaucoma following congenital cataract surgery (GFCS). Methods: A retrospective, single-center, descriptive study was conducted on consecutive children diagnosed with GFCS who underwent PGI implantation between July 2022 and November 2023 at the University Medical Center Mainz. The primary outcome measure was the reduction in IOP at the last follow-up visit. Results: Ten eyes of nine children were included in the study. The mean follow-up time was 7.70 ± 4.22 months (4.68–10.72 months). At the end of the study follow-up, the mean (95% CI) reduction in IOP was −14.8 ± 8.73 mmHg (−8.56 to −21.04 mmHg, p < 0.001). At the last follow-up, 30.0% (3/10) of patients achieved an IOP (intraocular pressure) of ≥6 and ≤21 mmHg with a reduction in IOP of ≥25% without treatment, while 90.0% (9/10) achieved this target IOP regardless of glaucoma medication treatment. The mean number of antiglaucoma medications was significantly reduced from 3.50 (IQR = 1) to 2.0 (IQR = 2, p = 0.01), and the visual acuity logMAR improved from 1.26 ± 0.62 to 1.03 ± 0.48 (p = 0.04). Only one eye experienced numerical hypotony (4 mmHg) without choroidal detachment or anterior chamber shallowing within the first 24 h. No other adverse events were observed during the follow-up period. Conclusions: PGI implantation significantly lowered IOP and the number of antiglaucoma eye drops with a favorable safety profile in children diagnosed with GFCS, thereby achieving a high rate of qualified surgical success in the short term. [ABSTRACT FROM AUTHOR]

Keratoconus eyes develop corneal decompensation more often compared to eyes with primary congenital glaucoma (PCG) following Descemet's membrane (DM) tear. This study was conducted to compare the posterior corneal morphology in areas with DM breaks with regards to DM and pre-Descemet's layer (PDL) between the two. In this cross-sectional comparative study, anterior segment optical coherence tomography (AS-OCT) scans of the posterior cornea of advanced keratoconus eyes with hydrops (n = 12), PCG eyes with Haab's striae (n = 15), and healthy control eyes (n = 14) were compared for DM-PDL morphology. These were further corroborated by the histopathology of corneal buttons from keratoconus (n = 14) and PCG (n = 13) cases obtained following penetrating keratoplasty and compared with controls (enucleated retinoblastoma globes, n = 6) on light microscopy and collagen IV immunostaining. AS-OCT showed a thicker median DM/PDL complex in PCG (80 µm) versus keratoconus eyes (36 µm, P = 0.01; Kruskal-Wallis test). The median height and length of detached DM-PDL were significantly more in keratoconus versus PCG (145 µm, 1766.1 ± 1320.6 µm vs. 26.5 µm, 453.3 ± 303.2 µm, respectively, P = 0.012; Kruskal-Wallis test). Type-1 DM/PDL detachment (seen as a characteristic taut chord) in keratoconus (90%) was the most common morphological pattern versus intracameral twin protuberance (92%) following DM breaks in PCG. Histopathology confirmed thicker DM in PCG (median: 63.4 µm) versus keratoconus eyes (median: 33.2 µm) or controls (27.1 µm) (P = 0.001; Kruskal-Wallis test). Greater height/length of DM/PDL detachment compounded by poor healing response (lower DM/PDL thickness) probably causes more frequent corneal decompensation in keratoconus eyes when compared to PCG eyes following DM tears. [ABSTRACT FROM AUTHOR]

BACKGROUND: There have been studies on the use of cognitive behavioral nursing intervention (CBNI) but the main subjects were patients with secondary glaucoma and there are fewer studies on the care of congenital glaucoma. OBJECTIVE: To explore the clinical value of cognitive behavioral nursing model in patients with congenital glaucoma. METHODS: One hundred and fifty-three postoperative patients with congenital glaucoma treated in our hospital between January 2021 and December 2022 were prospectively selected for the study and randomly divided into a control group (n = 77) and an observation group (n = 76). The control group was given routine nursing, and the observation group was given cognitive behavioral nursing mode on the basis of the control group. Anxiety self-assessment scale (SAS), depression self-assessment scale (SDS), Connor-Davidson toughness scale, and treatment adherence evaluation scale were used to evaluate the psychological state, mental toughness, treatment adherence, treatment effect and nursing care satisfaction in the two groups before and after 2 weeks of intervention. The efficacy of the treatment was also assessed by determining the visual acuity (VA), intraocular pressure (IOP), and mean defective (MD) value of the visual field of the two groups of patients. RESULTS: After nursing, the SDS score (46.33 ± 6.16 versus 53.21 ± 5.94) and SAS score (44.41 ± 5.6 versus 52.82 ± 6.31) in the observation group were lower than those in the control group (P < 0.05). The scores of optimism (11.55 ± 1.90 versus 8.20 ± 1.95), self-improvement (22.05 ± 3.60 versus 17.60 ± 4.30), tenacity (37.45 ± 3.10 versus 28.90 ± 4.55) and total score (71.35 ± 8.00 versus 56.85 ± 8.50) in the observation group were higher than those in the control group (P < 0.05). After care, the VA of the observation group (0.95 ± 0.22) was greater than that of the control group (0.84 ± 0.16), and the IOP (14.25 ± 0.58 versus 15.89 ± 0.67) and the MD (5.42 ± 0.46 versus 6.68 ± 0.49) of the observation group were less than that of the control group. The difference between the two groups was statistically significant (P < 0.05). The compliance (96.05% versus 85.71%) and nursing satisfaction (96.10% versus 85.71%) of the observation group were higher than those of the control group (P < 0.05). CONCLUSION: Cognitive-behavioural nursing care for glaucoma patients can improve patients' mental toughness, improve visual acuity, reduce intraocular pressure and mean visual field defect values, and have a positive effect on enhancing patients' treatment adherence and nursing satisfaction. [ABSTRACT FROM AUTHOR]

A 6-month-old female infant with megalophthalmos was referred with the suspicion of congenital glaucoma. Refractive measurements obtained with handheld autorefractometry were −7.00 −2.00 × 90° in the right eye and −6.00 −2.00 × 100° in the left eye and ultrasonic axial lengths were 22.50 mm in both eyes. Intraocular pressures and vertical and horizontal corneal diameters of the proband were 11 mm Hg, 11 mm, and 11.50 mm in both eyes, respectively. She was diagnosed as having early-onset high myopia. Her father also had degenerative high myopia (−12.00 diopters) in the right eye, bilateral congenital lens opacities, and retinal detachment in the left eye. Her mother was emmetropic with normal eye examination results. Clinical exome sequencing analysis revealed a novel ENST00000380518.3 c.3528_3530 delins GACCATTAGCA (Chr12:48369813: GCA > TGCTAATGGTC) variant in the collagen type II alpha 1 chain (COL2A1) on chromosome 12q13 (OMIM 108300), consistent with the Stickler syndrome type 1. Subsequent segregation analysis revealed paternal inheritance. Although many pathogenic null variants have been described within the COL2A1 gene, there is currently no documented literature pertaining to this specific variant, making this the inaugural report of its manifestation in scientific discourse. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e23–e27.] [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the quality, reliability, technical quality, and readability of online information related to childhood glaucoma. Methods: In this cross-sectional study, no human subjects were studied. Analysis was done for online websites on childhood glaucoma. The terms "childhood glaucoma," "pediatric glaucoma," "congenital glaucoma," "buphthalmos," and "big eyes" were entered into the Google search engine and the first 100 search results were assessed for quality, reliability, technical quality, and readability. Peer-reviewed articles, patient forum posts, dictionary definitions, and websites that appeared as targeted ads, were not in English, or were not focused on humans were excluded. Each website was evaluated for (1) quality and reliability using the DISCERN, HONcode, and JAMA criteria; (2) technical quality assessing 11 technical aspects; and (3) readability using six separate criteria (Flesch-Kincaid Reading Ease Score and Grade Level, Gunning Fog Index score, the Simple Measure of Gobbledygook Index, Coleman–Liau Index, and Automated Readability Index). Results: The median scores for the DISCERN, HONcode, and JAMA criteria were 2.6 (range = 1 to 4.75; 1 = worst, 5 = best), 10 (range = 0 to 16; 0 = worst, 16 = best), and 2 (range = 0 to 4; 0 = worst, 4 = best), respectively. The median technical quality score was 0.7. Readability was poor among most websites, with a median Flesch-Kincaid grade Grade Level Score of 9.3. The median Gunning Fog Index score was 9.8. There was a statistically significantly higher JAMA score and Gunning Fog Index score among the private websites compared to the institutional websites. However, institutional websites had higher technical quality. Conclusions: Online information on childhood glaucoma had poor to moderate quality and reliability. The technical quality is good; however, most websites' readability was above the recommended 5th to 6th grade reading level. [J Pediatr Ophthalmol Strabismus. 2024;61(3):198–203.] [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical characteristics and outcomes of a pediatric cohort surgically treated for primary or secondary pediatric glaucoma (PPG/SPG). Methods: A retrospective chart review was conducted of all patients with pediatric glaucoma who had surgery between 2013 and 2021. Relevant demographic and clinical data were cumulated and analyzed. Results: Forty-two eyes of 29 patients (18 girls and 11 boys) were included: 22 (52.4%) primary congenital glaucoma (PCG), 7 (16.7%) juvenile open-angle glaucoma, and 13 (30.9%) SPG. Mean ages at presentation were 2.57 ± 2.87, 131.96 ± 27.71, and 62.09 ± 65.12 months, respectively. In this study, eyes with PCG presented the earliest, with the highest intraocular pressure (IOP) and thickest central corneal thickness (CCT). The mean number of glaucoma surgeries was 1.48 ± 0.71, with 38.1% of the eyes needing two or more glaucoma surgeries; trabeculectomy was the most frequent glaucoma surgery in this cohort. After surgical intervention, the overall mean IOP dropped from 32.25 ± 12.97 to 18.10 ± 9.23 mm Hg (P <.001). Moreover, the percentage using antiglaucoma medications decreased from 100% to 35.7% at the final visit, as did the number of medications prescribed per eye (2.69 ± 0.92 vs 1.05 ± 1.46, P ≤.001). Mean best corrected visual acuity (BCVA), in patients who could have their BCVA measured, improved from 0.61 ± 0.61 to 0.53 ± 0.51 logMAR at final follow-up. Conclusions: Surgical intervention was shown to provide a well-controlled IOP, decrease dependance on glaucoma medications, and improve BCVA in both PPG and SPG. Multiple surgical interventions may be necessary in the treatment of some pediatric patients with glaucoma. Prognostically, thicker CCT was significantly associated with worse IOP control, more glaucoma surgeries, and more antiglaucoma medications at the final visit. Initial BCVA correlated significantly with BCVA at the final visit. [J Pediatr Ophthalmol Strabismus. 2024;61(3):188–197.] [ABSTRACT FROM AUTHOR]

Primary congenital glaucoma is a rare disease that occurs in early birth and can lead to low vision. Evaluating affected children is challenging and there is a lack of studies regarding color vision in pediatric glaucoma patients. This cross-sectional study included 21 eyes of 13 children with primary congenital glaucoma who were assessed using the Farnsworth D-15 test to evaluate color vision discrimination and by spectral domain optical coherence tomography to measure retinal fiber layer thickness. Age, visual acuity, cup-to-disc ratio and spherical equivalent data were also collected. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were measured and compared based on color vision test performance. Four eyes (19%) failed the color vision test with diffuse dyschromatopsia patterns. Only age showed statistical significance in color vision test performance. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were similar between the color test outcomes dyschromatopsia and normal. While the color vision test could play a role in assessing children with primary congenital glaucoma, further studies are needed to correlate it with damage to retinal fiber layer thickness. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the surgical outcomes of pediatric glaucoma in a cohort of Indian population. Materials and Methods: We conducted a single-center retrospective study including pediatric glaucoma patients who had undergone surgery between January 2012 and January 2022. The surgeries performed were trabeculectomy with mitomycin-C or Ologen, combined trabeculectomy with trabeculotomy (CTT), Ahmed glaucoma valve (AGV) implantation, and diode laser transscleral cyclophotocoagulation. Success was defined as complete if intraocular pressure (IOP) was between 6 and 21 mmHg in children who were examined on slit lamp, or between 6 and 18 mmHg in patients examined under general anesthesia, in the absence of any glaucoma medication and as qualified, with glaucoma medication at the last follow-up. Outcome measures included IOP at the last follow-up, number of glaucoma medications, any complications, and additional surgeries. Results: Seventy-eight eyes of 68 children were included. The most common glaucoma types were primary congenital glaucoma (30.8%), followed by posttraumatic glaucoma (17.9%) and postvitreoretinal surgery glaucoma (16.7%). The mean IOP reduced from 34.17 ± 9.35 mmHg preoperatively to 21.38 ± 9.61 mmHg at the last follow-up (P < 0.001). The number of glaucoma medications reduced from 2.55 ± 1.10 preoperatively to 1.76 ± 1.26 at the last follow-up (P < 0.001). Success was achieved in 62.8% of eyes and the mean survival time was 3.62 years. Among all procedures, AGV implantation had a longer survival time (mean 4.86 years). Conclusion: Pediatric glaucoma management remains a challenge. Majority of the cases remain refractory in spite of multiple surgical interventions. AGV and CTT could be offered as primary surgery in cases of pediatric glaucoma with hazy cornea where goniotomy may not be an option. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the current practice, equipment availability, and training needs for managing childhood glaucoma in Nigeria. Materials and Methods: An online questionnaire (Google Forms) was distributed through E-mails and social media platforms of pediatric ophthalmologists and glaucoma specialists who practice in Nigeria and manage glaucoma in children aged 0-16 years. Information concerning sociodemographic characteristics, type of practice, location of practice, years of practice, status, and preferred practices in the management of childhood glaucoma cataracts were obtained and analyzed with SPSS. Results: Thirty (23.3%) out of 129 eligible participants indicated they perform glaucoma surgeries in children. The majority (66.6%) had practiced as specialists for 10 years or less, and 70% were pediatric ophthalmologists. A third of the respondents practiced in the country's southwest region, with none in the Northeast region. The most common surgery performed for primary congenital glaucoma was combined trabeculotomy trabeculectomy, while trabeculectomy was the most common surgery performed for juvenile open-angle glaucoma. Two respondents reported performing glaucoma drainage device surgery and seven reported possessions of skills for goniotomy. All centers had trabeculectomy instrument sets, while three centers had facilities for endolaser cyclophotocoagulation, and only two centers had knives for goniotomy. Antimetabolites were routinely used for childhood glaucoma surgeries by 26 (86.7%) respondents, and the most common antimetabolite used was mitomycin (21; 80.8%). Conclusion: There is a need for the development of in-country training programs and the exchange of skills through collaboration among those providing glaucoma services within Nigeria to improve the care of children with glaucoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify the pathogenic alleles in primary congenital glaucoma patients for early cure of the disease METHODOLOGY: A cross-sectional descriptive study was carried out after approval from the ethical committee of SIOVS from December 2022 to November 2023 at Sindh Institute of Ophthalmology & Visual Sciences, Hyderabad. The consanguineous pedigree consisting of more than one affected was included, and the pedigree consists only one affected or secondary cause of vision loss was excluded. After getting informed consent, ten cc blood samples from all available participants in the pedigree were drawn, and DNA was extracted. The ARMS Assay and Sanger sequencing methods were adapted to analyze the CYP1B1 gen. RESULTS: In the present study, one novel c.1187C>T, p.Pro396Leu and one reported c.1169G>A, p.Arg390His allele in CYP1B1 gene were found in two isolated pedigrees enrolled from Sindh Pakistan. ARMS Assay method and the Sanger sequencing method were adopted to detect pathogenic variants. Bioinformatics tools were used to analyze the pathogenesis of identified alleles and compare phenotype -genotype correlation. CONCLUSION: The findings of novel and frequently reported mutations have a significant role in advancing genetic testing protocols, enabling more accurate targeting of diagnoses and identified alleles that may be added to existing repositories of the genetic database. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the anterior segment structures using ultrasound biomicroscopy (UBM) in primary congenital glaucoma (PCG) and explore their correlation with disease severity and surgical outcomes. Methods: Clinical information of PCG patients who underwent UBM prior to their first glaucoma surgeries from September 2014 to March 2021 were reviewed. The study included 214 UBM images of 154 PCG eyes and 60 fellow unaffected eyes. Anterior segment characteristics were analyzed. UBM parameters, including the iris thickness (IT) at variant distances from the pupil edge and iris root, anterior chamber depth (ACD), and pupil diameter (PD), were compared between two groups and their relationship with clinical factors and surgical outcomes were analyzed in PCG eyes. Results: PCG eyes had unclear scleral spur, thin iris, wide anterior chamber angle, deep anterior chamber, rarefied ciliary body, elongated ciliary processes, and abnormal anterior iris insertion. ITs were thinner, ACD was deeper, and PD was larger in PCG eyes than fellow unaffected eyes (all P < 0.001). In PCG eyes, thinner ITs correlated with bilateral involvement and earlier age at presentation, and larger PD correlated with earlier age at presentation (P = 0.030) and higher intraocular pressure (P < 0.001). Thinner IT2 (P = 0.046) and larger PD (P = 0.049) were identified as risk factors for surgical failure. Conclusion: UBM is a powerful technique to exam anterior segment structures in PCG. The anatomical features are associated with disease severity and surgical outcomes, providing essential clinical insights. [ABSTRACT FROM AUTHOR]

Keratoconus eyes develop corneal decompensation more often compared to eyes with primary congenital glaucoma (PCG) following Descemet’s membrane (DM) tear. This study was conducted to compare the posterior corneal morphology in areas with DM breaks with regards to DM and pre-Descemet’s layer (PDL) between the two. In this cross-sectional comparative study, anterior segment optical coherence tomography (AS-OCT) scans of the posterior cornea of advanced keratoconus eyes with hydrops (n = 12), PCG eyes with Haab’s striae (n = 15), and healthy control eyes (n = 14) were compared for DM–PDL morphology. These were further corroborated by the histopathology of corneal buttons from keratoconus (n = 14) and PCG (n = 13) cases obtained following penetrating keratoplasty and compared with controls (enucleated retinoblastoma globes, n = 6) on light microscopy and collagen IV immunostaining. AS-OCT showed a thicker median DM/PDL complex in PCG (80 µm) versus keratoconus eyes (36 µm, P = 0.01; Kruskal–Wallis test). The median height and length of detached DM–PDL were significantly more in keratoconus versus PCG (145 μm, 1766.1 ± 1320.6 μm vs. 26.5 μm, 453.3 ± 303.2 μm, respectively, P = 0.012; Kruskal–Wallis test). Type-1 DM/PDL detachment (seen as a characteristic taut chord) in keratoconus (90%) was the most common morphological pattern versus intracameral twin protuberance (92%) following DM breaks in PCG. Histopathology confirmed thicker DM in PCG (median: 63.4 μm) versus keratoconus eyes (median: 33.2 µm) or controls (27.1 μm) (P = 0.001; Kruskal–Wallis test). Greater height/length of DM/PDL detachment compounded by poor healing response (lower DM/PDL thickness) probably causes more frequent corneal decompensation in keratoconus eyes when compared to PCG eyes following DM tears.

Aim The goal of this study is to assess the effectiveness of implantation of an Ahmed glaucoma valve (AGV) augmented with the use of mitomycin-C (MMC) and preserved amniotic membrane (AM), as a first line of intervention in cases of advanced primary congenital glaucoma (PCG). Patients and methods Prospective clinical and interventional trial was done on 30 eyes of 24 patients, aged between 6 months and 3 years, with advanced PCG at presentation. AGV (model FP8) implantation augmented with use of MMC and two layers of cryopreserved human AM as a primary intervention. Results At all-time intervals (at day 1, 1, 3, and 12 months following surgery), the postoperative intraocular pressures (IOPs) were significantly lower than the preoperative IOPs (16.83±2.78 mmHg at month 12 compared with a preoperative IOP of 38.29±4.23 mmHg). At all times, the postoperative corneal diameter was not noticeably smaller than the preoperative values (13.79±0.57 mm at month 12 compared with preoperative value of 13.93±0.58 mm). Conclusion AGV augmented with the use of MMC and AM can be considered as a secure and reliable approach for management of cases of advanced PCG, without additional risks compared with other techniques.

We present two siblings from consanguineous marriage, both with congenital glaucoma and seizure disorders with progressive visual impairment and blindness. The pedigree showed that five (one male and four females) of the eleven siblings have varied degrees of visual impairment to blindness with seizure disorders. To the best of our knowledge, familial congenital glaucoma with epilepsy has not been reported, hence the communication to highlight this unusual condition which could be an association or syndromic.

Objectives: The objectives of this study were to (i) evaluate the prevalence of pre-iridal monocellular and fibrovascular membranes in canine globes affected with congenital glaucoma associated with anterior segment dysgenesis (ASD), primary glaucoma associated with goniodysgenesis (GD), and secondary glaucoma, and (ii) examine the associations between monocellular and fibrovascular membranes by breed, gender, age and histopathologic ocular changes on light microscopic examination. Methods: Records of dogs who had eyes enucleated due to blindness and uncontrolled glaucoma were reviewed. Glaucoma was categorized clinically and histologically into three groups: congenital/ASD, primary/GD, and secondary glaucoma. The presence or absence and type of pre-iridal membrane (monocellular or fibrovascular) and other intraocular histologic findings were reviewed and compared statistically for each group. Results: In total, 108 canine globes (101 dogs) were included. Pre-iridal monocellular membranes were identified with light microscopy in 10 out of 19 congenital/ASD, 29 out of 40 primary, and 23 out of 49 secondary glaucoma globes. Fibrovascular membranes were observed in 3 out of 19 congenital/ASD, 9 out of 40 in primary, and 24 out of 49 secondary glaucoma globes. There were no associations between the type of membrane and breed, gender, or age. Peripheral anterior synechiae were more common in globes with fibrovascular membranes, and uveal atrophy was more common in globes with monocellular membranes. Conclusion: Pre-iridal monocellular membranes are common in all types of canine glaucoma. They are identified with light microscopy most easily in cases of primary glaucoma, and they are masked by pre-iridal fibrovascular membranes in other forms of glaucoma. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the short-term efficacy of cyclocryotherapy in pain control in 63 patients with absolute glaucoma who had pain and no vision despite maximum medical treatment. Methods: 63 eyes of 63 glaucoma patients defined as absolute glaucoma were included in the study. The intraocular pressures, number of drops used, pain status and need for recurrent therapy were compared before and after the procedure at 1 and 3 months Results: 13 of the patients were female and 40 were male. The mean age was 59.4±17.5 years. 50 of the patients were diagnosed with neovascular glaucoma, 3 with congenital glaucoma, 1 with primary open-angle glaucoma and 9 with angle-closure glaucoma. Preoperative mean intraocular pressure was 50.7±12 mmHg, while it was found to be 37.9±15.4 mmHg in the 1st month and 28.5±15.8 mmHg in the 3rd month postoperatively. The decrease in intraocular pressure before and after the procedure was statistically significant at 1 and 3 months. (p<0.0001) Pain control was received 85% at the first month and 96% at the third month after the procedure. Number of medications that were used was found 3.00 and 2.3±0.9 respectively before and after the procedure and this was statistically significant. (p<0.0001) While no phthisis was observed in any patient, evisceration was applied to 2 patients because of uncontrolled pain. Conclusion: Cyclocryotherapy may be a preferred treatment option before evisceration, as it is a non-invasive, inexpensive and easily applicable method in patients whose pain control cannot be achieved, although it has lost its former popularity with the discovery of new options in the surgical and medical treatment of glaucoma [ABSTRACT FROM AUTHOR]

Purpose: To predict the presence of angle dysgenesis on anterior-segment optical coherence tomography (ADoA) by using deep learning (DL) and to correlate ADoA with mutations in known glaucoma genes. Participants: In total, 800 high-definition anterior-segment optical coherence tomography (AS-OCT) images were included, of which 340 images were used to build the machine learning (ML) model. Images used to build the ML model included 170 scans of primary congenital glaucoma (16 patients), juvenile-onset open-angle glaucoma (62 patients), and adult-onset primary open-angle glaucoma eyes (37 patients); the rest were controls (n = 85). The genetic validation dataset consisted of another 393 images of patients with known mutations that were compared with 320 images of healthy controls. Methods: ADoA was defined as the absence of Schlemm's canal, the presence of hyperreflectivity over the region of the trabecular meshwork, or a hyperreflective membrane. DL was used to classify a given AS-OCT image as either having angle dysgenesis or not. ADoA was then specifically looked for on AS-OCT images of patients with mutations in the known genes for glaucoma. Results: The final prediction, which was a consensus-based outcome from the three optimized DL models, had an accuracy of >95%, a specificity of >97%, and a sensitivity of >96% in detecting ADoA in the internal test dataset. Among the patients with known gene mutations, (MYOC, CYP1B1, FOXC1, and LTBP2) ADoA was observed among all the patients in the majority of the images, compared to only 5% of the healthy controls. Conclusion: ADoA can be objectively identified using models built with DL. [ABSTRACT FROM AUTHOR]

Purpose: To analyze primary congenital glaucoma (PCG) anterior chamber and angle anomalies over 360° as possible biomarkers of severity and prognosis. Methods: A cross-sectional observational study was conducted analyzing anterior segment anomalies of PCG patients over 4 years of age who underwent trabeculectomy combined with trabeculotomy and age-matched controls using anterior segment optical coherence tomography (ASOCT), CASIA-2. Anterior iridotrabecular adhesions or anterior iris insertion was identified and quantified from the scleral spur using the iridotrabecular contact (ITC) index parameter as a surrogate. Results: There was a variable but significantly increased anterior iridotrabecular adhesion on ITC index, ITC area, corneal volume, anterior chamber volume, iris volume, anterior chamber depth, and small/absent trabecular meshwork in PCG eyes compared to control eyes. In PCG eyes, anterior iridotrabecular adhesion had a positive correlation with pre-operative central corneal thickness (CCT) (r = 0.53, P = 0.02), review iris thickness (r = 0.4, P = 0.04), and ITC area (r = 0.85, P < 0.001). Review iris thickness had a negative correlation with pre-operative vertical cup-disc ratio (r = -0.51, P = 0.008). Iris hypoplasia with fewer or absent folds, collarette, pupillary ruff, and pupillary ruff to collarette distance was significantly different from controls. Conclusion: ASOCT in PCG eyes has shown that they have variable anterior iridotrabecular tissue adhesions, anomalous tissue/membranes in the angle, and iris hypoplasia correlating with pre-operative cup-disc ratio. These features could be used as gonioscopic and clinical biomarkers to assess the severity and prognosis of the disease. The presence of abnormal iris morphology and iridotrabecular tissue anomalies in PCG suggests that it is more than just isolated trabeculodysgenesis and is probably best considered as part of the anterior segment dysgenesis spectrum. [ABSTRACT FROM AUTHOR]

Background: This retrospective study aimed to evaluate the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in Chinese patients with primary congenital glaucoma (PCG) and identify factors influencing surgical success. Methods: Fourteen patients (24 eyes) diagnosed with PCG who underwent gonioscopy-assisted transluminal trabeculotomy were recruited, and data on intraocular pressure (IOP), antiglaucoma medication, surgery-related complications, and additional treatments were collected during preoperative and postoperative visits. Surgical success was defined as IOP ≤ 21 mmHg and a reduction of > 30% from baseline, with (partial success) or without (complete success) antiglaucoma medication. Results: Mean preoperative IOP was 30.41 ± 6.09 mmHg. At the final visit, mean IOP reduction was 16.1 ± 9.1 mmHg (52%), and 19 of 24 eyes were topical medication–free. IOP was significantly decreased at each postoperative visit compared with baseline (P < 0.05 for all time points). Cumulative proportions of complete and partial success were 79.2% and 95.8%, respectively, at three years postsurgery. Patients without prior antiglaucoma procedures, without postoperative IOP spikes, and those undergoing complete trabeculotomy exhibited improved surgical prognosis. No permanent vision-threatening complications occurred in the 24 eyes by the end of the respective follow-ups. Conclusion: Gonioscopy-assisted transluminal trabeculotomy emerged as a safe and effective procedure for PCG treatment, characterized by outstanding IOP reduction efficacy and high surgical success rates. [ABSTRACT FROM AUTHOR]

Many forms of childhood glaucoma have been associated with underlying genetic changes, and variants in many genes have been described. Currently, testing is variable as there are no widely accepted guidelines for testing. This systematic review aimed to summarize the literature describing genetic changes and testing practices in childhood glaucoma. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) 2020 guidelines and registered with Prospero (ID CRD42023400467). A comprehensive review of Pubmed, Embase, and Cochrane databases was performed from inception through March 2, 2023 using the search terms: (glaucoma) AND (pediatric OR childhood OR congenital OR child OR infant OR infantile) AND (gene OR genetic OR genotype OR locus OR genomic OR mutation OR variant OR test OR screen OR panel). Information was extracted regarding genetic variants including genotype-phenotype correlation. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1,916 records screened, 196 studies met inclusion criteria and 53 genes were discussed. Among study populations, mean age±SD at glaucoma diagnosis was 8.94±9.54 years and 50.4% were male. The most common gene discussed was CYP1B1, evaluated in 109 (55.6%) studies. CYP1B1 variants were associated with region and population-specific prevalence ranging from 5% to 86% among those with primary congenital glaucoma. MYOC variants were discussed in 31 (15.8%) studies with prevalence up to 36% among patients with juvenile open angle glaucoma. FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation. Overall risk of bias was low; the most common domains of bias were selection and comparability. Numerous genes and genetic changes have been associated with childhood glaucoma. Understanding the most common genes as well as potential genotype-phenotype correlation has the potential to improve diagnostic and prognostic outcomes for children with glaucoma. [ABSTRACT FROM AUTHOR]

Introduction: Primary congenital glaucoma causes vision loss if intraocular pressure is uncontrolled. Nonpenetrating deep sclerectomy is effective in treating primary congenital glaucoma. However, the effects of inadvertent trabeculodescemetic window perforation remain unclear. Methods: This retrospective cohort study included patients with primary congenital glaucoma who underwent nonpenetrating deep sclerectomy between 2014 and 2021. The perforation group had intraoperative trabeculodescemetic window perforations; the non-perforation group did not. The primary outcome was intraocular pressure between the groups over 15 months. The secondary outcomes included surgical success and complications. Results: The study included 74 eyes of 44 patients. The cohort comprised 31 perforated and 43 non-perforated eyes. Both groups showed significant intraocular pressure reduction without significant between-group differences in complete (68 vs. 77%), qualified (19 vs. 9%), or failed (13 vs. 14%) treatments. The median intraocular pressure decreased from 39 to 14 mmHg in the perforation group and 35 to 12 mmHg in the non-perforation group. Of the 74 treated eyes, 68 (92%) showed no complications. Conclusions: An inadvertent trabeculodescemetic window perforation during nonpenetrating deep sclerectomy for primary congenital glaucoma did not significantly affect intraocular pressure outcomes compared to non-perforated cases over 15 months. Nonpenetrating deep sclerectomy reduced intraocular pressure regardless of intraoperative perforation in patients with primary congenital glaucoma. Perforation of the trabeculodescemetic window was associated with a low incidence of postoperative complications. [ABSTRACT FROM AUTHOR]

Introduction: Micropulse cyclophotocoagulation (MPCPC) has been shown in adults to offer a favorable post-operative safety profile compared to continuous wave transscleral cyclophotocoagulation (CWCPC) in the management of glaucoma. The purpose of this study is to evaluate the long term efficacy, safety, and effectiveness of MPCPC in the management of pediatric glaucoma when compared to CWCPC. Methods: IRB approved retrospective chart review of patients with pediatric glaucoma that underwent MPCPC and CWCPC at 2 separate institutions. Success was defined as intraocular pressure (IOP) between 5 and 21mmHg on any number of topical glaucoma medication without requiring additional surgical intervention or oral IOP lowering medication. Results: Of the 48 patients in the study, 22 (26 eyes) underwent MPCPC and 26 (30 eyes) underwent CWCPC. At 1 year, 7 out of 26 eyes (26.9%) achieved success in the MPCPC group compared to 13 out of 30 eyes (43.3%) in the CWCPC group. Survival analysis unveiled a statistically significant difference in success between the two groups (p = 0.03). Conclusion: In pediatric glaucoma patients undergoing cyclophotocoagulation procedures, CWCPC outperformed MPCPC using default settings in terms of achieving long-term IOP control. Additional studies are required to evaluated augmented MPCPC settings in pediatric glaucoma patients. [ABSTRACT FROM AUTHOR]

Purpose To identify the pattern(s) in using antiglaucoma medications following glaucoma surgery in children and compare their efficacies. Methods Retrospective chart review of patients (≤12 years) receiving glaucoma surgery from January 2013 to December 2020. Partially responsive patients needing antiglaucoma medications to attain an Intraocular pressure (IOP) of at least 18 mmHg were divided into three groups: (A) received beta-blocker (β-Blockers); (B) received Prostaglandin analogues and (C) received fixed β-Blocker+ Carbonic anhydrase inhibitor (CAI) preparation. Data included demographics, clinical characteristics, IOP (before, after 1 month, and at last follow-up), and surgeries. Successful treatment attained IOP less than or equal to 18 mmHg on last follow-up. Side effects were recorded. Results Totally 200 eyes of 152 patients were included, (61%) presented within the first month of life, 54% were males, 31.6% had bilateral disease and (82.2%) had primary congenital glaucoma (PCG). Pre-treatment IOP was significantly higher in group C (P=0.009). The most common procedure performed was trabeculotomy (P=0.014). After a mean follow-up period of 20.12 months, all three groups showed a significant reduction in the IOP (P≤0.001), with the highest percent reduction attained in group C (43.7% vs. 33.4% and 33.1% in groups A and B, respectively) P=0.001. Final success rates were 41.2%, 83.3%, and 82.2% for groups A, B, and C, respectively. Dry eye was the most common side effect (32 eyes) mainly occurring in group A (21.6%). Conclusions The most frequently used antiglaucoma medications following partially successful surgery are CAI+β-Blocker combinations. They seem to have the most potent effect and are usually used as a first line the higher the initial IOP is. [ABSTRACT FROM AUTHOR]

Aim The goal of this study is to assess the effectiveness of implantation of an Ahmed glaucoma valve (AGV) augmented with the use of mitomycin-C (MMC) and preserved amniotic membrane (AM), as a first line of intervention in cases of advanced primary congenital glaucoma (PCG). Patients and methods Prospective clinical and interventional trial was done on 30 eyes of 24 patients, aged between 6 months and 3 years, with advanced PCG at presentation. AGV (model FP8) implantation augmented with use of MMC and two layers of cryopreserved human AM as a primary intervention. Results At all-time intervals (at day 1, 1, 3, and 12 months following surgery), the postoperative intraocular pressures (IOPs) were significantly lower than the preoperative IOPs (16.83±2.78 mmHg at month 12 compared with a preoperative IOP of 38.29±4.23 mmHg). At all times, the postoperative corneal diameter was not noticeably smaller than the preoperative values (13.79±0.57 mm at month 12 compared with preoperative value of 13.93±0.58 mm). Conclusion AGV augmented with the use of MMC and AM can be considered as a secure and reliable approach for management of cases of advanced PCG, without additional risks compared with other techniques. [ABSTRACT FROM AUTHOR]

Corneal haze, due to edema or opacity, is a major contraindication for performing ab interno angle surgeries such as goniotomy in children with primary congenital glaucoma (PCG), despite otherwise favorable surgical outcomes expected in these patients. In this case series involving patients of PCG with moderate corneal haze, the authors describe a technique for performing goniotomy in cases with compromised visibility by using indocyanine green (ICG) to aid in the visualization of angle structures. The authors used 0.2% ICG intracamerally, which stained the anterior and posterior trabecular meshwork (TM) with different intensities, before proceeding with goniotomy. The junction between the two zones was discernible due to the contrast imparted by ICG staining, despite poor visibility, allowing the surgeon to incise the TM at the correct site. The possibility of performing goniotomy in such patients with the help of ICG can revolutionize our surgical approach to patients with PCG and corneal edema.

Neonatal diabetes and congenital hypothyroidism (CH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLIS3 gene. Small for gestational age, congenital glaucoma, polycystic kidney disease, cholestatic hepatic fibrosis, pancreatic exocrine insufficiency, developmental delay, dysmorphic facial features, sensorineural deafness, osteopenia, and skeletal anomalies are other accompanying phenotypic features in the 22 cases described so far. We present a male patient with neonatal diabetes, CH, congenital glaucoma, developmental delay, and facial dysmorphism. During the patient’s 17-year follow-up, no signs of exocrine pancreatic insufficiency, liver and kidney diseases, deafness, osteopenia, and bone fracture were observed. A homozygous exon 10-11 deletion was detected in the GLIS3 gene. We report one of the oldest surviving GLIS3 mutation case with main findings of neonatal diabetes and CH syndrome to contribute to the characterization of the genotypic and phenotypic spectra of the syndrome.