Development of the anterior segment of the eye requires reciprocal sequential interactions between the arising tissues, facilitated by numerous genetic factors. Disruption of any of these processes results in congenital anomalies in the affected tissue(s) leading to anterior segment disorders (ASD) including aniridia, Axenfeld-Rieger anomaly, congenital corneal opacities (Peters anomaly, cornea plana, congenital primary aphakia), and primary congenital glaucoma. Current understanding of the genetic factors involved in ASD remains incomplete, with approximately 50% overall receiving a genetic diagnosis. While some genes are strongly associated with a specific clinical diagnosis, the majority of known factors are linked with highly variable phenotypic presentations, with pathogenic variants in FOXC1, CYP1B1, and PITX2 associated with the broadest spectrum of ASD conditions. This review discusses typical clinical presentations including associated systemic features of various forms of ASD; the latest functional data and genotype-phenotype correlations related to 25 ASD factors including newly identified genes; promising novel candidates; and current and emerging treatments for these complex conditions. Recent developments of interest in the genetics of ASD include identification of phenotypic expansions for several factors, discovery of multiple modes of inheritance for some genes, and novel mechanisms including a growing number of non-coding variants and alleles affecting specific domains/residues and requiring further studies.

Primary congenital glaucoma (PCG), a developmental glaucoma occurring due to angle anomaly, earns growing concerns among ophthalmologists for its vision-damaging attribute. The incidence of PCG varies among races and geographic regions and is mostly genetically associated. Theories have been posed in attempt to address the etiology of this congenital maldevelopment and in the meanwhile providing evidence for feasibility of PCG surgeries. In regard to the clinical aspects of this entity, both the clinical characteristics and general principals of management are introduced, with angle surgeries highlighted for clarifying details including their success rates, key points for a successful surgical intervention, postoperative management, and follow-up strategies. Taking patients\' vision-associated quality of life into consideration, we stressed that further perceptual learning and low vision rehabilitation are momentous. However, much has yet to be elucidated in respect of the truly comprehensive pathogenesis underneath as well as means by which clinical outcomes of PCG can be further improved. We are now looking forward to innovative therapeutic approaches like gene therapy in specific genes in the future, with the hope of improving their life-long visual quality in those young patients.

OBJECTIVE: To evaluate the safety and efficacy of the PAUL Glaucoma Implant (PGI) for managing refractory primary congenital glaucoma (PCG) over a one-year period.
METHODS: 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%.
CONCLUSIONS: 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.

Primary congenital glaucoma (PCG) is one of the leading causes of visual damage and blindness, severely affecting the quality of life of affected children. It is characterized by cupping of the optic disc and loss of ganglion cells due to elevated intraocular pressure. While most PCG patients exhibit epiphora, photophobia, and buphthalmos with corneal opacity, variability in phenotypic manifestations is not uncommon. Prompt diagnosis and treatment of PCG affected individuals becomes relevant to preserve visual function throughout their lives. Most PCG cases are sporadic or autosomal recessive; however, an incompletely dominant autosomal dominant form arising from mutations in the TEK gene has recently been demonstrated. Here, we describe the clinical and mutational features of a cohort of Mexican patients with TEK-related PCG. Our results support the involvement of the TEK gene as an important cause of the disease in our ethnic group and expand the mutational spectrum causing PCG by reporting 10 novel disease-causing variants.

UNASSIGNED: To describe the inheritance pattern and clinical variability of primary congenital glaucoma (PCG) in a family with two affected siblings.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.
CONCLUSIONS: 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.

OBJECTIVE: To report on the outcome of subsequent interventions after failed initial intervention for primary congenital glaucoma (PCG).
METHODS: Retrospective chart review of children presenting with PCG and failed the initial glaucoma surgery in Alexandria Main University Hospital from 2005 to 2017. The data included demographics, preoperative, operative and postoperative clinical characteristics. Success was defined as IOP<16mmHg and <20% from the presenting IOP and C/D ratio like or better than presentation.
RESULTS: The charts of 531 (260 right, 49%) eyes of 360 (224 males, 62%) children presenting with PCG and failed the initial glaucoma surgery (58 [31 right, 53%] eyes [10.9%] of 50 [28 males, 56%] children) revealed that at initial presentation, the mean±standard deviation (range, median) of the age of the children subjected to one successful glaucoma procedure and the study children was 8.6±11.7 (0.6-109, 5.2) and 4.9±6.1 (0.5-34.4, 3.0) months, respectively. Each of the study eyes was subjected to 2.6±0.8 (2-5.2) glaucoma procedures. The mean±standard deviation (range, median) duration between the initial and second glaucoma surgery and the duration of follow-up was 6.9±7.8 (0.7-39,3.9) and 61.5±32.1 (12.0-139.1, 60.1) months, respectively. At the final follow-up visit success was reported in 41 (70.1%) eyes by IOP<16mmHg criterion, 39 (67.2%) eyes by IOP>20% reduction criterion and in 28 (out of 35 eyes, 80.0%) by the optic nerve condition (C/D ratio) criterion. Success by all 3 criteria was reported in 25 (out of 35 eyes, 71%) eyes.
CONCLUSIONS: A repeat glaucoma surgical procedure maybe needed in up to 11% of operated PCG eyes, with the subsequent glaucoma surgical procedures being successful by about 70%.

BACKGROUND: Childhood glaucoma is a major cause of childhood blindness worldwide. The profile of childhood glaucoma has not been well characterized in sub-Saharan Africa. Thus, this study was designed to describe demographics, clinical features, managements of childhood glaucoma, and improvements in visual acuity (VA) and intraocular pressure (IOP) from baseline to final visit.
METHODS: This retrospective study included glaucoma patients below 18 years old who were diagnosed between September 2019 to August 2022. Childhood glaucoma diagnosis and classification was made as per the Childhood Glaucoma Research Network Classification (CGRN).
RESULTS: A total of 105 children (181 eyes) were diagnosed with glaucoma. The most common type of childhood glaucoma was primary congenital glaucoma (PCG) constituting (42%, n = 76 eyes, 95% confidence interval (CI), 34.7-49.5%; P = 0.037), followed by glaucoma suspect (22.1%, n = 40 eyes, 95% CI, 16.3-28.9%; P < 0.001) and juvenile open-angle glaucoma (JOAG) (15.5%, n = 28 eyes, 95% CI, 10.5-21.6%; P < 0.001). While the most common type of secondary glaucoma was steroid-induced glaucoma, followed by glaucoma following cataract surgery. Bilateral glaucoma was found in 72.4% (n = 76 children, 95% CI, 62.8-80.7%; P < 0.001) of children. In both primary and secondary glaucoma, boys were affected more than girls, in ratio of 2:1 and 2.7:1, respectively. The mean age at presentation for patients with PCG was 2.7 years. Close to 93.4% (71) of PCG eyes were managed surgically, of which majority underwent combined trabeculotomy and trabeculectomy (CTT). Most of secondary glaucoma cases were treated medically. Overall, 85.3% (111) of eyes had successful control of IOP ≤ 21 mmHg.
CONCLUSIONS: PCG was the most common type of childhood glaucoma. One of a well-recognized challenge in developing countries, late presentation of patients with PCG, was also observed in our study. Which highlights, the need of increasing access to eye-care service and awareness of childhood glaucoma as a major public health issue. Steroid-induced glaucoma was the most common type of secondary glaucoma; appropriate measures should be taken to prevent this preventable glaucoma.

OBJECTIVE: To describe three anterior segment dysgenesis disorders with infantile corneal opacities, namely, congenital hereditary endothelial dystrophy (CHED), primary congenital glaucoma (PCG), and Peters anomaly (PA) in terms of clinical characteristics, histopathology, genetic association, and diagnostic imaging profiles using imaging modalities such as ultrasound biomicroscopy (UBM) and microscope-integrated intraoperative optical coherence tomography (i-OCT).
METHODS: Seventy-four eyes with 22 eyes of CHED, 28 eyes of PA, and 24 eyes of PCG were clinically evaluated and underwent imaging using UBM and i-OCT. Corneal buttons of 16 operated patients underwent histopathological analysis, while genetic analysis was done in 23 patients using whole-exome sequencing.
RESULTS: Corneal diameters (CD) and UBM parameters like anterior chamber depth (ACD), iris thickness (IT), and ciliary body (CB) thickness revealed a statistically significant difference between the three categories. In PA, 9 eyes had a third rare phenotype with only a posterior corneal defect with no iris adhesions. Genetic mutations were seen in all tested patients with CHED, in 83.3% of patients with PCG, and in 80% of patients with the third type of PA. i-OCT helped in the characterization of corneal opacity, identification of posterior corneal defects, iridocorneal adhesions, and contour of Descemet\'s membrane.
CONCLUSIONS: Overlapping phenotypes of the above disorders cause a diagnostic dilemma and parameters like CDs, UBM ACD, IT, and CB thickness help differentiate between them. i-OCT can help in classifying the diseases in a high resolution, non-contact manner, and can better delineate corneal characteristics. The rare third type of PA phenotype may have a genetic association.

Primary congenital glaucoma (PCG) occurs worldwide and has a broad range of ocular manifestations. It poses a therapeutic challenge to the ophthalmologist. A proper diagnostic evaluation under anesthesia is advisable for all children who do not cooperate for an office examination. Medical therapy only serves as a supportive role, and surgical intervention remains the principal therapeutic modality. Angle incision surgery such as goniotomy or trabeculotomy ab externo is the preferred choice of surgery in the Caucasian population. Primary combined trabeculotomy-trabeculectomy with or without antifibrotic therapy is the preferred choice in certain regions such as India and the Middle East where the disease usually presents with severe forms of corneal edema along with megalocornea. In refractory cases, trabeculectomy with antifibrotic therapy or glaucoma drainage devices are available options in the armamentarium. Cycloablative procedures should be reserved for eyes with poor visual potential. Myopia is common among children with PCG, and appropriate optical refractive correction in the form of glasses or contact lenses should be provided. Amblyopia therapy should be instituted to ensure overall visual development in the early developmental years. Low-vision rehabilitation services should be provided to children with vision impairment. Long-term follow-up is mandatory and carers of children with PCG should be counseled and educated about this need. Regardless of the visual outcomes, clinicians should emphasize the need for education of these children during the clinic visit. The overall goal of the management should be to improve the overall quality of life of the children with PCG and their carers.