Macular and peripapillary vascular parameters in the fellow eyes of unilateral primary congenital glaucoma: a comparative study.

PURPOSE: To study the fellow eyes of patients with unilateral primary congenital glaucoma (PCG) using optical coherence tomography angiography (OCTA) and compare them to normal age- and refractive error-matched healthy controls. METHODS: Using OCTA, the foveal avascular zone (FAZ) area, cup:disk ratio, vessel density (VD) of the optic nerve head (ONH) and peripapillary area and the macular VD in superficial (SCP) and deep vascular complexes in both 3 mm and 6 mm scans of both groups were compared. Clinical data included best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP), anterior and posterior segments examination findings, including ONH cup:disk ratio. RESULTS: A total of 48 eyes of 48 children (24 eyes in each group) were included. There was no difference in the mean retinal nerve fiber layer thickness, cup:disk ratio, baseline visual acuity, or spherical equivalent between groups (P > 0.05). In the 3 mm macular scan, the VD of the SCP at the fovea was significantly higher in the PCG group compared to controls (P = 0.04). In the ONH scans, there was a significantly reduced inside the disk VD in the PCG group compared to controls (P = 0.03). There was no significant difference in other macular and ONH vascular parameters between groups (P > 0.05). CONCLUSIONS: In our study cohort, there was no difference in most of the macular and ONH vascular parameters between groups. However, the fellow eyes of PCG patients exhibited higher VD of the SCP at the fovea and reduced inside the disk VD compared with control eyes.

Comparative posterior corneal profile of keratoconus hydrops versus Haab's striae in congenital glaucoma.

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.

Neonatal-Onset Congenital Ectropion Uveae May Be Caused by a Distinct CYP1B1 Pathologic Variant.

PURPOSE: To report underlying genetic variants of recently described distinct phenotype of newborn glaucoma: neonatal-onset congenital ectropion uveae (NO-CEU). DESIGN: Prospective cohort study. METHODS: Setting: tertiary care teaching institute. SUBJECTS: Thirteen children with clinical diagnosis of NO-CEU who had completed 1-year follow-up after glaucoma surgery and had undergone clinical exome sequencing (CES) by selective capture and sequencing of the protein-coding regions of the genes including 19 candidate genes for NO-CEU were assessed. The same criteria were applied for evaluating pathogenicity of variants to all the candidate genes. OUTCOME MEASURES: primary-genetic variants found on CES keeping in view the clinical indication of congenital glaucoma; secondary-corneal clarity and intraocular pressure (IOP) at baseline and 1-year follow-up, interventions required to control IOP, and postoperative visual acuity. The genetic variants were correlated with the outcome. RESULTS: All 13 patients diagnosed with NO-CEU had onset of glaucoma at birth and severe bilateral disease. Twelve of 13 (92.3%) patients harbored CYP1B1 variants. Nine of these 12 patients (83.3%) were homozygous for [c.1169G>A(p.Arg390His)] in exon-3 of CYP1B, with 5 common homozygous single-nucleotide polymorphisms flanking the pathogenic variant. They had intractable glaucoma and required multiple surgeries. Six patients had persistent corneal opacities, necessitating optical iridectomies. Three patients were compound heterozygous for CYP1B1 variants, showing [c.1169G>A(p.Arg390His)] along with [c.1103G>A(p.Arg368His)], [c.1103G>A (p.Arg368His)] along with [c.1403_1429dup(p.Arg468_Ser476dup)], and [(c.1063C>T(p.Arg355Ter)] along with [c.1325del(p.Pro442GlnfsTer15)]. These patients had better visual outcomes. CONCLUSIONS: NO-CEU appears to be a phenotypic marker for specific CYP1B1 genotypes, one of which is [c.1169G>A(p.Arg390His)] in our study population. Phenotype recognition is helpful to characterize the underlying genetic variants.

A Service Coverage Analysis of Primary Congenital Glaucoma Care Across the United States.

PURPOSE: To assess the number of infants at risk of delayed primary congenital glaucoma (PCG) evaluation due to long travel times to specialists. DESIGN: Cross-sectional geospatial service coverage analysis. METHODS: All American Glaucoma Society (AGS) and American Association for Pediatric Ophthalmology and Strabismus (AAPOS) provider locations were geocoded using each organization's member directory. Sixty-minute drive time regions to providers were generated using ArcGIS Pro (Esri). The geographic intersection of AGS and AAPOS service areas was computed because patients typically require visits to both types of specialists. American Community Survey data were then overlaid to estimate the number of infants within and beyond the AGS/AAPOS service areas. RESULTS: One thousand twenty-nine AGS and 1,040 AAPOS provider locations were geocoded. The analysis yielded 944,047 infants age 0-1 year (23.6%) who live beyond the AGS/AAPOS service areas. Therefore, approximately 14-94 new PCG cases/year may be at risk of delayed diagnosis as a result of living in a potential service desert. Compared with children living within the AGS/AAPOS service areas, children aged <6 years in these potential service deserts were more likely to live in households earning below the US federal poverty level, lack health insurance, and live in a single-parent home. These communities are disproportionately likely to experience other rural health disparities and are more prevalent across the Great Plains. CONCLUSION: Service coverage analysis is a useful tool for identifying underserved regions for PCG referrals and evaluation. These data may assist in targeting screening programs in low access areas for pediatric glaucoma care.

Follow-up Adherence and Barriers to Care for Pediatric Glaucomas at a Tertiary Care Center.

PURPOSE: To determine the percent adherence to follow-up for patients with pediatric glaucomas seen at a tertiary care center and to elucidate risk factors. DESIGN: Retrospective cohort study. METHODS: Patients with pediatric glaucomas seen at the University of Minnesota over 8.5 years were classified as adherent, nonadherent, or lost to tertiary follow-up if they followed up within 0-30 days, between 31 and 180 days, or later than 180 days of the recommended appointment time or never, respectively. RESULTS: Of 176 patients analyzed, 95 (54%) were adherent (51% male; mean [standard deviation (SD)] age: 56.1 [59.8] months), 5 (3%) were nonadherent (20% male; mean [SD] age: 25.0 [35.8] months), and 76 (43%) were lost to tertiary follow-up (55% male; mean [SD] age: 58.9 [53.1] months). Multiple logistic regression analysis of variables that were significant in isolation revealed that only race (white: odds ratio, 3.58; 95% confidence interval, 1.42-9.05; P = .007) and distance from the eye clinic (per 50 miles: odds ratio, 0.79; 95% confidence interval, 0.67-0.92; P = .003) significantly impacted adherence. CONCLUSIONS: This is the first study of adherence to follow-up recommendations for patients with pediatric glaucomas. Percent adherence to follow-up appointments was alarmingly low, and decreased adherence was observed with non-white race and increased distance to the eye clinic. Physicians should consider these risk factors when risk-stratifying patients with pediatric glaucomas for nonadherence to follow-up. Additional studies to improve adherence through interventions that reduce biases and barriers to follow-up are needed.

Neonatal-Onset Congenital Ectropion Uveae: A Distinct Phenotype of Newborn Glaucoma.

PURPOSE: To describe neonatal-onset congenital ectropion uveae (N-CEU) as a distinct clinical entity of newborn glaucoma (NG) and to study its significance toward the severity and outcome of NG. DESIGN: Prospective clinical cohort study. METHODS: The study took place at a tertiary care postgraduate teaching institute. It included consecutive patients with NG who presented between July 1, 2016 and September 30, 2017, with a minimum postoperative follow-up of 1 year. Infants with any ocular anomaly apart from CEU were excluded. Patients with N-CEU were compared with those with neonatal-onset primary congenital glaucoma (N-PCG). All infants underwent goniotomy or trabeculotomy, with trabeculectomy depending on corneal clarity. Clinical features at presentation and outcome 1 year after surgery were defined as good or satisfactory if intraocular pressure was ≤16.0 mm Hg under anesthesia without or with topical medications, respectively, and poor if the infant required additional surgery. RESULTS: Twenty eyes of 10 patients with N-CEU were compared with 16 eyes of 9 patients with N-PCG. Infants with N-CEU had significantly worse corneal clarity (mean grade 2.0 ± 0.7 vs 1.4 ± 0.8; P = .026) and poorer outcomes compared with those with N-PCG. Seven of 16 (43.7%) eyes with N-PCG had a cornea clear enough at presentation for a goniotomy compared with only 2 of the 20 (10%) eyes with N-CEU (P = .026). Thirteen of 16 (81.2%) eyes with N-PCG had a good or satisfactory outcome compared with 6 of 20 (30%) eyes with N-CEU (P = .001). CONCLUSIONS: N-CEU appears to be distinct from the unilateral CEU in older patients described in the literature and may be considered a poorer prognosis phenotype of neonatal-onset glaucoma.

SVEP1 as a Genetic Modifier of TEK-Related Primary Congenital Glaucoma.

Purpose: Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss by the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploinsufficiency accounts for 5% of PCG in diverse populations, with low penetrance explained by variable dysgenesis of Schlemm's canal (SC) in mice. We report eight families with TEK-related PCG, and provide evidence for SVEP1 as a disease modifier in family 8 with a higher penetrance and severity. Methods: Exome sequencing identified coding/splice site variants with an allele frequency less than 0.0001 (gnomAD). TEK variant effects were assayed in construct-transfected HEK293 cells via detection of autophosphorylated (active) TEK protein. An enucleated eye from an affected member of family 8 was examined via histology. SVEP1 expression in developing outflow tissues was detected by immunofluorescent staining of 7-day mouse anterior segments. SVEP1 stimulation of TEK expression in human umbilical vascular endothelial cells (HUVECs) was measured by TaqMan quantitative PCR. Results: Heterozygous TEK loss-of-function alleles were identified in eight PCG families, with parent-child disease transmission observed in two pedigrees. Family 8 exhibited greater disease penetrance and severity, histology revealed absence of SC in one eye, and SVEP1:p.R997C was identified in four of the five affected individuals. During SC development, SVEP1 is secreted by surrounding tissues. SVEP1:p.R997C abrogates stimulation of TEK expression by HUVECs. Conclusions: We provide further evidence for PCG caused by TEK haploinsufficiency, affirm autosomal dominant inheritance in two pedigrees, and propose SVEP1 as a modifier of TEK expression during SC development, affecting disease penetrance and severity.

Acute Hydrops in the Fellow Eye of Infants with Primary Congenital Glaucoma after Intraocular Pressure Reduction in 1 Eye.

PURPOSE: To demonstrate the occurrence of acute hydrops in the fellow eye of infants with primary congenital glaucoma (PCG) treated for glaucoma in 1 eye. DESIGN: Small, observational case series. PARTICIPANTS: Three infants with PCG who demonstrated acute hydrops in the fellow eye after treatment of the worse eye. METHODS: Intraocular pressure (IOP) was lowered surgically in 2 infants and medically in 1 infant with PCG. Two infants underwent combined trabeculotomy with trabeculectomy, and goniotomy was possible in 1 infant. MAIN OUTCOME MEASURES: Observation of the fellow eye after lowering IOP in an eye with acute hydrops. RESULTS: Two infants underwent glaucoma surgery in 1 eye and demonstrated acute hydrops in the fellow eye within 1 week. The third infant demonstrated acute hydrops after medically controlling IOP in 1 eye before the scheduled surgery. After surgical treatment, the stromal edema cleared completely in all 3 infants, leaving behind a small area of opacity where the Descemet's tear had healed. CONCLUSIONS: Our report demonstrates that the fellow eye of a patient with PCG may be at risk of sudden raised IOP resulting in acute hydrops, and early treatment may help to prevent this phenomenon in the fellow eye.

Primary Congenital Glaucoma: Trends in Presentation Over 3 Decades at a Tertiary Eye Care Center in India.

PRECIS: In this study, huge time delay was observed between first primary congenital glaucoma (PCG) symptom recognition by parents to ophthalmological diagnosis and this delay was unchanged over time. Bilateral affliction and mean presenting intraocular pressure (IOP) remained unaltered. PURPOSE: To compare the trends in presentation of patients with PCG over 3 different time periods at 10-year intervals (1998, 2008, and 2018) managed by a single surgeon at one of the largest tertiary eye care centers in South India. METHODS: Retrospective analysis of 313 eyes of 172 patients diagnosed to have PCG and treated at the L V Prasad Eye Institute (LVPEI) between January and December of the 3 specified years. Data collected included age at symptom recognition and at presentation, sex, affected eye, signs and symptoms, time between onset of symptoms and diagnosis (diagnostic delay), corneal clarity, and IOP. RESULTS: Of the 172 patients, 48 (27.9%), 76 (44.2%), and 48 (27.9%) belonged to 1998, 2008, and 2018, respectively. Bilateral affliction (79% to 84%) was common and there was no sex predilection. The median age at recognition of first symptoms by caregivers/parents was 1 day (interquartile range, 1 to 30), and at diagnosis was 120 days (interquartile range, 30 to 378). Overall, presentation to LVPEI was delayed by >3 months in 80 (46.5%) children, and there was no statistically significant difference in the duration of delay over time (P=0.13). There was no significant difference in the mean presenting IOP over time (P>0.05). CONCLUSIONS: We provide unique single center-based information of trends in the presentation of patients with PCG over 3 decades. Diagnostic delay was common, and a large number of characteristics of patients with PCG in South India have remained unchanged, particularly, age at onset and at diagnosis and laterality.

Paediatric glaucoma in Scotland.

BACKGROUND: The primary aim was to estimate the incidence of primary and secondary childhood glaucoma in Scotland over a 2-year period. The secondary aim was to gauge the confidence and experience of ophthalmologists in Scotland in managing these patients. METHODS: A 7 question electronic survey was distributed to all consultant members of the Scottish Paediatric Club and Scottish Glaucoma Club. Respondents were asked to report the number of cases and types of childhood glaucoma they had managed in the last 2 years. Respondents were also asked about experience and confidence in a range of glaucoma procedures, number of patients requiring referral to specialist centres and interest in the development of a centre of excellence in Scotland. RESULTS: The survey returned a 56% response rate, reporting 85 new cases of paediatric glaucoma in Scotland over the preceding 2 years. 11 (12.9%) had primary glaucoma and 74 (87.1%) had secondary glaucoma. The most common subtype of secondary glaucoma was uveitic glaucoma (n = 29). None of the respondents declared confidence or experience in trabeculotomy or goniotomy procedures. Eleven children required referral to a specialist unit outside Scotland. 85.7% of respondents felt Scotland would benefit from a specialist unit for paediatric glaucoma. CONCLUSIONS: This survey reflects an appetite for a specialist service for paediatric glaucoma in Scotland. However, further consideration is needed to determine if there is sufficient patient load to maintain such a service.

Choroidal neovascular membrane associated with primary congenital glaucoma and buphthalmos.

An 18-year-old man with primary congenital glaucoma and buphthalmos in both eyes presented with unilateral, sudden-onset, painless vision loss. He had previously undergone multiple sectoral ab externo rigid-probe trabeculotomy in both eyes and subsequently Baervelt glaucoma implantion in both eyes, with adequate intraocular pressure control. Examination revealed subfoveal choroidal neovascular membrane (CNVM) and associated hemorrhages in the right eye. He was treated with 3 consecutive, monthly, intravitreal injections of bevacizumab and recovered baseline vision.

Micropulsed diode laser cyclophotocoagulation in recurrent pediatric glaucoma.

PURPOSE: To evaluate the intermediate-term efficacy and safety of micropulsed diode laser cyclophotocoagulation in recurrent pediatric glaucoma. PATIENTS AND METHODS: A prospective interventional study included children <16 years old diagnosed with recurrent glaucoma, attending Mansoura University, during the period from July 2017 to November 2017. Micropulsed diode laser sessions were performed in all the cases. The main outcome was the intraocular pressure reduction with monitoring of complications as secondary outcome. The mean follow-up period was 15.08 ± 1.1 (mean: 12-16) months. RESULTS: A total of 36 eyes of 29 patients were included (62% males) with median age of 24 months. Primary congenital glaucoma represented 47.2% of the initial diagnoses. At the 15th month, the mean intraocular pressure dropped significantly from 37.5 ± 11.3 mmHg at baseline to 20.03 ± 2.7 mmHg (p < 0.001) with 37.15% reduction. The mean number of glaucoma medications decreased significantly from 2.6 ± 0.5 pretreatment to 1.7 ± 0.6 at the 15th month (p < 0.001). A total of 24 eyes (66.7%) required second session of treatment with mean number of 1.7 ± 0.5 sessions per eye. The cumulative probability of qualified success was 69.4%, 58.3%, 52.8%, 47.2%, and 41.7% at 1, 3, 6, 12, and 15 months after treatment. Qualified success was achieved in 61% at 15 months without statistically significant difference between the initial diagnoses (p = 0.61). None of the eyes developed any major ocular complications throughout the follow-up period. CONCLUSION: Micropulsed diode laser was proved to be a safe approach with relative effectiveness in controlling intraocular pressure in children with recurrent glaucoma.

A Rare Case Report of Frank Ter Haar Syndrome in a Sibling Pair Presenting With Congenital Glaucoma.

Frank Ter Haar syndrome (FTHS) is a rare autosomal recessive disorder with characteristic skeletal, cardiac, ocular, and craniofacial abnormalities. We report a sibling pair presenting with clinical features typical of FTHS, born to consanguineous parents, with a novel mutation in the SH3PXD2B gene on chromosome 5q35.1 that results in premature truncation of the protein encoded. The children presented with brachycephaly, multiple joint contractures, cardiac valvular defects, bilateral megalocornea, and congenital glaucoma. Trabeculotomy combined with trabeculectomy was performed in both siblings to control intraocular pressure. The characteristic clinical features with the underlying genetic defects confirmed the diagnosis of FTHS. Early diagnosis and treatment of congenital glaucoma preserved vision in the children.

Primary congenital glaucoma in Denmark, 1977-2016.

PURPOSE: To perform an epidemiological survey of all patients in Denmark diagnosed with primary congenital glaucoma (PCG) from 1977 to 2016. METHODS: A retrospective, nationwide study based on a review of medical files of all children with PCG born in Denmark from 1977 to 2016. PCG was defined as glaucoma due to isolated angle dysgenesis affecting children from birth and including late onset/late recognized PCG, excluding glaucoma associated with other congenital abnormalities. Incidence and risk factors of PCG including gender, consanguinity, family history, ethnicity, comorbidity and prematurity were evaluated and stratified by decade (1977-1986, 1987-1996, 1997-2006 and 2007-2016). Age at first symptoms, age at diagnosis, age at time of first surgery and possible diagnostic delay were assessed. RESULTS: Of 118 patients were identified, annual incidence of PCG was 4.8 per 100 000 live born. 62.3% of cases were bilateral. The relative risk (RR) of PCG was significantly higher in boys (62.7% of patients, RR 1.60 (95% CI 1.10-2.32)). 13.6% had comorbidity. Median age at time of first symptoms was 75 days, median age at time of diagnosis was 150 days and median diagnostic delay was 75 days with no significant difference throughout the decades. Unilateral cases presented symptoms and were diagnosed significantly later than bilateral cases. CONCLUSION: We provide unique nation-based information on the incidence of PCG from a single country covering 40 years. Male gender was a risk factor. Diagnostic delay was unchanged throughout the 4 decades and a high percentage of comorbidity was revealed. Introducing a standardized paediatric screening of all PCG children should be considered.

Congenital choroidal melanocytoma in a child with ocular melanocytosis.

A 1-day-old child was brought to the clinic for evaluation of enlarged right eye (OD). On examination, OD showed buphthalmos with diffuse scleral melanocytosis, fleshy blackish-brown extrascleral mass with corneal extension, and secondary glaucoma. Anterior segment evaluation revealed darkly pigmented iris and fundus evaluation OD revealed a darkly pigmented choroidal lesion. The left eye was within normal limits. A clinical diagnosis of choroidal melanocytoma with ocular melanocytosis was made. Enucleation OD followed by orbital implant was performed. Histopathology showed features of diffuse ocular melanocytosis involving limbus, iris, ciliary body, choroid, sclera, optic nerve head, optic nerve sheath, along with choroidal melanocytoma with extrascleral tumour extension. We presume that choroidal melanocytoma may have arisen from ocular melanocytosis.

Childhood Glaucoma: Long-Term Outcomes of Glaucoma Drainage Device Implantation Within the First 2 Years of Life.

PRéCIS:: Glaucoma drainage device (GDD) implantation within the first 2 years of life yields an overall success rate of 59.0% at 5 years. It is safe and requires a relatively low number of postoperative interventions. PURPOSE: The purpose of this study was to evaluate the long-term outcomes of the treatment of childhood glaucoma with GDDs within the first 2 years of life. METHODS: A total of 43 children (60 eyes) having undergone GDD implantation within the first 2 years of life at Moorfields Eye Hospital between July 2005 and November 2014 were included in this retrospective case series. Kaplan-Meier survival curves were created for the evaluation of surgical success. Log-rank analysis was performed for the detection of risk factors for failure. MAIN OUTCOME MEASURES: Overall success rates at 1, 5, and 7 years after surgery. Surgical success: intraocular pressure ≥5/≤21 mm Hg, no further glaucoma surgery required, nonoccurrence of loss of perception of light or devastating complications. RESULTS: The results are listed as follows: Median duration of follow-up was 48.0 months. Median age at surgery was 11.5 months. Seventy-three percentage of children were white. Most common types of glaucoma were primary congenital glaucoma [(PCG); 67%], glaucoma following cataract surgery (18%), and anterior segment dysgenesis (10%). Overall success rates were 93%, 59%, and 59%, respectively. There were no differences in the survival rates as a function of PCG/non-PCG, sex, and removal of intraluminal stent suture. Mean number of general anesthesia administrations during the first postoperative year was 1.8. CONCLUSIONS: GDD implantation within the first 2 years of life is effective and safe. The low number of general anesthesia administrations required during the first postoperative year could help to reduce the burden placed on children and carers. Further research is required to directly compare the efficiency of GDD implantation with other surgical options.