A Case of Non-Syndromic Congenital Cataracts Caused by a Novel MAF Variant in the C-Terminal DNA-Binding Domain-Case Report and Literature Review.

The MAF gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the MAF variants in the C-terminal DNA-binding domain associated with non-syndromic congenital cataracts and describe a patient with a novel, disease-causing de novo missense variant. Published reports of C-terminal MAF variants and their associated congenital cataracts and ophthalmic findings were reviewed. The patient we present and his biological parents had genetic testing via a targeted gene panel followed by trio-based whole exome sequencing. A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in MAF, NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified. We report the novel missense variant, c.922A>G (p.Lys308Glu), in the C-terminal DNA-binding domain of MAF classified as likely pathogenic and associated with non-syndromic bilateral congenital cataracts.

Factors and outcomes associated with corneal edema and Haabs striae in primary congenital glaucoma.

PURPOSE: To identify specific factors and outcomes associated with corneal edema and Haabs striae in primary congenital glaucoma (PCG). METHODS: The medical records of patients with PCG from 2011 to 2023 with >3 months' follow-up were reviewed retrospectively. Preoperative details and final outcomes were compared between eyes with and without corneal findings. The right eye of bilateral cases and the affected eye in unilateral cases were included. RESULTS: A total of 58 patients (104 eyes, 69% male) underwent initial angle surgery at an average age of 297 ± 368 (median, 134) days. Corneal edema and Haabs striae were present preoperatively in 72 (69%) eyes of 41 patients and 68 (65%) eyes of 39 patients, respectively. Patients with corneal edema presented at a younger age (P < 0.0001) and with shorter axial length (P = 0.01) than those without edema. Univariate analysis showed that corneal edema was associated with worse visual acuity at final follow-up (OR = 4.4; 95% CI, 1.2-25.3). Patients with Haabs striae were older than those without striae (P = 0.04). After angle surgery, corneal edema was present at 1 month in 71% (95% CI, 52-84), at 2 months in 26% (95% CI, 12-42), at 3 months in 16% (95% CI, 6-30), and at 1 year in 3% (95% CI, 0-13). Corneal opacification did not resolve in 4 eyes of 3 patients after >4 years of follow-up. CONCLUSIONS: In our study cohort, corneal edema resolved in the majority of PCG cases within 2-3 months of initial angle surgery but was associated with younger age at presentation and worse visual acuity at final follow-up.

Concurrent adjacent strabismus surgery with glaucoma drainage device placement in childhood glaucomas.

BACKGROUND: Determine outcomes of concurrent strabismus surgery with placement of a glaucoma drainage device (GDD) in children. METHODS: Retrospective review of pediatric patients who underwent simultaneous lateral rectus (LR) muscle surgery with superotemporal GDD placement. Strabismus and GDD success were defined as residual horizontal misalignment < 10 prism diopter (PD) and intraocular pressure (IOP) < 21 mmHg, no visually devastating complications, and no additional IOP-lowering surgeries. RESULTS: Fifteen eyes of 13 patients (69% male) underwent LR surgery (14 recessions, 1 resection) for exotropia or esotropia simultaneous with GDD placement (13 Baerveldt, 2 Ahmed) at 8.34 ± 5.26 years. Preoperative visual acuity (VA) in operative eye (0.89 ± 0.54) was worse than non-operative eye (0.23 ± 0.44, p = 0.0032). Preoperative horizontal deviation was 38.3 ± 9.4 PD and LR recession was 7.4 ± 1.1 mm. At final follow-up, VA in operative eye (0.87 ± 0.52) was unchanged from preoperative (p = 0.4062). Final IOP was significantly decreased (12.4 ± 4.7 mmHg vs. 31.1 ± 11.4 mmHg, p = 0.0001) as was number of glaucoma medications (2.7 ± 1.7 vs. 1.1 ± 1.3, p = 0.0037). Five (38%) and 9 patients (69%) met criteria for strabismus and GDD success, respectively. Two eyes required tube revision and endoscopic cyclophotocoagulation and 2 eyes had additional strabismus surgery. CONCLUSIONS: Concurrent strabismus and GDD surgery decreased horizontal deviation and obtained IOP control. It is important to consider correction of strabismus at time of GDD placement to maximize visual development and improve cosmesis in children with glaucoma.

Outcomes of inferior oblique myectomy versus recession combined with lateral rectus recession in V-pattern exotropias.

PURPOSE: To compare outcomes of bilateral lateral rectus recession (BLRc) paired with either bilateral inferior oblique myectomy (BIOm) or bilateral inferior oblique recession (BIOc) to correct V-pattern exotropia. METHODS: The medical records of children (≤18 years) who underwent BLRc with BIOm or BIOc (10 mm) for V-pattern intermittent exotropia between December 2020 and May 2022 and who had at least 6 months' postoperative follow-up were reviewed. Outcomes included horizontal alignment, bilateral inferior oblique action, stereopsis, postoperative exotropia control score, and additional strabismus surgeries. Analysis was stratified by preoperative V pattern into subgroups of 10Δ-14Δ and ≥15Δ. RESULTS: Fifty patients underwent BLRc with BIOm (n = 26) or BIOc (n = 24), with no difference in age, sex, or follow-up length. Preoperatively, there were no differences in stereopsis, horizontal or vertical deviations in primary position, strabismus control, or inferior oblique overaction (IOOA). The BIOc group had greater preoperative V pattern than the BIOm group (18.1 ± 6.8 D vs 14.3 ± 7.0 D, resp. [P = 0.03]). There was no difference in BLRc surgical dose. At final follow-up (mean, 448 ± 189 days), both groups showed a postoperative decrease in horizontal deviation, amount of V pattern, and IOOA. For patients with ≥15Δ V pattern, BIOm decreased V pattern amount at distance (P = 0.02) and IOOA (P = 0.0035) more than BIOc, and BIOm patients had better control of residual strabismus at distance (P = 0.03) compared with the BIOc group overall, as well as for both V pattern subgroups. Two patients with BIOm and one with BIOc underwent additional strabismus surgery. CONCLUSIONS: BIOm or BIOc in combination with BLRc decreased the angle of exotropia and improved control. However, BIOm, especially with large V patterns, had a greater effect on decreasing the V pattern and IOOA and showed better control of residual strabismus.

Ophthalmological Manifestations of Axenfeld-Rieger Syndrome: Current Perspectives.

Axenfeld-Rieger syndrome (ARS) is a rare congenital disease that is primarily characterized by ocular anterior segment anomalies but is also associated with craniofacial, dental, cardiac, and neurologic abnormalities. Over half of cases are linked with autosomal dominant mutations in either FOXC1 or PITX2, which reflects the molecular role of these genes in regulating neural crest cell contributions to the eye, face, and heart. Within the eye, ARS is classically defined as the combination of posterior embryotoxon with iris bridging strands (Axenfeld anomaly) and iris hypoplasia causing corectopia and pseudopolycoria (Rieger anomaly). Glaucoma due to iridogoniodysgenesis is the main source of morbidity and is typically diagnosed during infancy or childhood in over half of affected individuals. Angle bypass surgery, such as glaucoma drainage devices and trabeculectomies, is often needed to obtain intraocular pressure control. A multi-disciplinary approach including glaucoma specialists and pediatric ophthalmologists produces optimal outcomes as vision is dependent on many factors including glaucoma, refractive error, amblyopia and strabismus. Further, since ophthalmologists often make the diagnosis, it is important to refer patients with ARS to other specialists including dentistry, cardiology, and neurology.

Ologen augmentation of Ahmed valves in pediatric glaucomas.

BACKGROUND: We previously showed that Ologen increased success and survival rates of Ahmed glaucoma devices in a small number of children. The current study analyzed the same surgical technique in an expanded cohort. METHODS: Retrospective interventional case series of children who underwent Ologen augmentation of Ahmed glaucoma device (OAGD) from 2018 to 2021 with ≥6 months' postoperative follow-up. Complete success was defined as intraocular pressure (IOP) of 5-20 mm Hg without glaucoma medications or additional IOP-lowering surgeries. Complete or qualified success was defined as above, except that IOP control was maintained with or without glaucoma medications. RESULTS: A total of 26 eyes of 18 patients underwent OAGD at a median age of 2.0 years. Diagnoses included primary congenital glaucoma (5 eyes) and glaucoma secondary to nonacquired ocular anomalies (9 eyes), nonacquired systemic anomalies (8 eyes), and acquired conditions (4 eyes). Seventeen eyes had ≥1 prior eye surgery (average, 1.6 ± 0.9 surgeries per eye). Preoperative IOP was 29.4 ± 9.9 mm Hg on an average of 2.7 ± 1.0 glaucoma medications. At final follow-up (1.3 ± 1.0 years; median 1.0), IOP (13.4 ± 4.7 mm Hg) and number of glaucoma medications (0.3 ± 0.7, median 0) were significantly decreased (P < 0.0001). Complete success was achieved in 77% of eyes (20/26); Kaplan Meier analysis showed 1- and 3-year survival rates of 82% (95% CI, 59-93) and 60% (95% CI, 25-83), respectively. Complete or qualified success was achieved in 100% of eyes (26/26) at final follow-up. There were no visually devastating complications. CONCLUSIONS: OAGD showed a high rate of success defined by decreased IOP and medication dependency in our study cohort of pediatric glaucoma patients.

Clinical outcomes and visual prognostic factors in congenital aniridia.

BACKGROUND: Evaluate outcomes and identify prognostic factors in congenital aniridia. METHODS: Retrospective interventional case series of patients with congenital aniridia treated between 2012-2020. Ocular examination and surgical details were collected. Surgical failure was defined as disease progression or need for additional surgery for same/related indication. Kaplan-Meier survival curves, Wilcoxon test, and univariate and multivariate linear regression analyses were performed. RESULTS: Ninety-four patients with congenital aniridia presented at median 19.0 years. Two-thirds of patients underwent ≥ 1intraocular surgery, with average of 1.7 ± 2.3 surgeries/eye. At final follow-up (median 4.0 years), 45% of eyes had undergone lensectomy. Aphakic eyes showed worse visual acuity (VA) than phakic or pseudophakic eyes. Glaucoma affected 52% of eyes, of which half required IOP-lowering surgery. Glaucoma drainage devices showed the highest success rate (71%) at 14.2 ± 15.4 years of follow-up. Keratopathy affected 65% of eyes and one-third underwent corneal surgery. Keratoprosthesis had the longest survival rates at 10-years (64% with 95% CI [32,84]). LogMAR VA at presentation and final follow-up were not statistically different. Half of patients were legally blind at final follow-up. Final VA was associated with presenting VA, glaucoma diagnosis, and cataract or keratopathy at presentation. Penetrating keratoplasty and keratoprosthesis implantation correlated with worse BCVA. CONCLUSIONS: Most aniridic patients in this large US-based cohort underwent at least 1 intraocular surgery. Cataract, glaucoma, and keratopathy were associated with worse VA and are important prognostic factors to consider when managing congenital aniridia.

Characteristics and Outcomes of Glaucoma Associated With Congenital Ectropion Uvea.

PURPOSE: To determine the visual outcomes and effectiveness of glaucoma surgeries in congenital ectropion uvea. DESIGN: Retrospective interventional case series. METHODS: Surgeries and examination findings were collected on 11 eyes of 8 patients with congenital ectropion uvea at 2 academic sites from 2001 to 2021. Visual outcomes, surgical success (intraocular pressure [IOP]: 5-20 mm Hg, no additional IOP-lowering surgery, no visually devastating complications), and survival rates of glaucoma surgeries were assessed. RESULTS: Glaucoma in bilateral congenital ectropion uvea was diagnosed at an earlier age (0.02 ± 0.01 years) than unilateral disease (8.9 ± 5.3 years, P = .002). All eyes required glaucoma surgery with 91% requiring multiple surgeries (3.5 ± 2.1, median 3 surgeries per eye). Trabeculotomy (8 eyes) showed 13% success rate. Although none of the 4 eyes that underwent trabeculectomy with mitomycin C needed repeat trabeculectomy, glaucoma drainage device placement, or cycloablation, 75% required bleb revision surgery. Glaucoma drainage devices (7 eyes) had a 57% success rate with 3 eyes requiring subsequent cycloablation (2) or trabeculectomy (1). At the final follow-up (8.5 ± 6.6 years, median: 7.9 years), all eyes achieved IOP control, and IOP was lower compared with presentation (13.2 ± 2.6 mm Hg vs 32.9 ± 9.9 mm Hg, P = .002). Best-corrected logarithm of the minimum angle of resolution visual acuity at the final follow-up was 0.2 ± 0.2. CONCLUSIONS: Bilateral congenital ectropion uvea presents with glaucoma earlier than unilateral cases. The majority of eyes required multiple glaucoma surgeries. Angle surgery was less effective than trabeculectomy or glaucoma drainage devices. IOP control was obtained in all eyes and affected individuals had good visual outcomes.

DDX58(RIG-I)-related disease is associated with tissue-specific interferon pathway activation.

BACKGROUND: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. METHODS: Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. RESULTS: We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. CONCLUSIONS: These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.

Outcomes of Baerveldt Glaucoma Drainage Devices in Pediatric Eyes.

PRCIS: In children, Baerveldt implants showed 84% success at 1 year, but decreased to 32% at 8 years. Age, race, and glaucoma type were not risk factors for failure. Concurrent intraocular surgery was associated with complications. PURPOSE: Evaluate success and risk factors for failure and complications of Baerveldt glaucoma implants in children. METHODS: Retrospective case series of children who underwent Baerveldt implant placement (2012-2019 by single surgeon) with ≥1 year follow-up. Ocular examination and surgical details were collected. Failure defined as intraocular pressure (IOP) <5 mm Hg or >21 mm Hg for 2 consecutive visits, need for IOP related surgery, or visually significant complication. RESULTS: One hundred-six eyes of 76 patients underwent 110 Baerveldt placement at median 6.4 years. Baerveldt placement was combined with additional procedures in 49% with vitrectomy most common (30%). Success of first Baerveldt (per patient) was 64% at final follow-up (median 4.7 y). One-, 5-, and 8-year survival rates were 84%, 60%, and 32%, respectively. There was no difference (P=0.97) in survival between first Baerveldt and all Baerveldt surgeries. Failure of first Baerveldt was not associated with sex, age, ethnicity, prior IOP-lowering surgery, concurrent intraocular surgery, or glaucoma type. Complications occurred in 14% and were associated with concurrent surgery. Twenty-six percent required additional IOP-lowering surgery. At final follow-up, IOP and glaucoma medications were significantly decreased (P<0.0001). Eyes underwent an average of 3.8±2.3 ocular surgeries and 3.0±2.0 glaucoma surgeries. CONCLUSIONS: Baerveldt implants showed good success initially, but survival rates declined over time. No risk factors for failure of first implanted Baerveldt were identified. Concurrent surgery was associated with complications. Majority of eyes required multiple surgeries to achieve IOP control and preserve vision.

Outcomes and surgical management of persistent fetal vasculature.

OBJECTIVE: To analyse outcomes in different forms of persistent fetal vasculature (PFV). METHODS AND ANALYSIS: Retrospective cohort study at a university-based practice of children presenting with PFV between 2011 and 2020. Exclusion criteria was surgical management outside of our institution and follow-up less than 1 month. Wilcoxon and Student's t-tests were used for statistical analysis. RESULTS: Forty-six eyes of 45 patients presented with PFV at 16.7±31.3 (median 2.8) months old with 32.6±29.8 (median 22.5) months of follow-up. Types of PFV included: mild combined anterior-posterior (23 eyes, 50%), severe combined anterior-posterior (18 eyes, 39%), severe anterior (3 eyes, 7%), mild anterior (1 eye, 2%) and posterior (1 eye, 2%). Thirty-two eyes (70%) underwent PFV surgical correction; lensectomy (13 mild combined), vitrectomy (3 mild combined), sequential lensectomy then vitrectomy (3 severe combined), combined lensectomy-vitrectomy (11 severe anterior or severe combined), laser retinopexy (1 mild combined). Five eyes required additional vitrectomy surgery for retinal detachment, fold or cyclitic membrane. Nine eyes developed glaucoma, six requiring Intraocular pressure (IOP)-lowering surgery. At final follow-up, 32 eyes had at least form vision and 6 eyes were aversive to light. Eight eyes, all which were severe combined, and four that did not undergo PFV surgery, were unable to detect light due to phthisis bulbi (7) and optic nerve hypoplasia (1). CONCLUSIONS: Classification of PFV is important in determining surgical approach with severe cases often requiring both lensectomy and vitrectomy for optimal anatomic and functional outcomes.

Ologen augmentation of Ahmed glaucoma drainage devices in pediatric glaucomas.

BACKGROUND: Limited data exists on the effectiveness of the collagen matrix, Ologen, on increasing Ahmed glaucoma valve (AGV) success in childhood glaucomas. METHODS: Ocular examination and surgical details of pediatric patients who underwent AGV placement ± Ologen augmentation between 2012 and 2020. Complete success was defined as intraocular pressure (IOP) between 5 and 20 mmHg without glaucoma medications and additional IOP-lowering surgeries. Qualified success was defined as above, except IOP control maintained with or without glaucoma medications. RESULTS: Twenty-two eyes of 16 patients underwent AGV placement of which 6 eyes had Ologen-augmentation (OAGV) and 16 eyes had conventional surgery (CAGV). Average age was 6.4 ± 5.1 years with 4.2 ± 2.5 follow-up years. There was no difference in age, number of previous surgeries, and preoperative IOP and glaucoma medications. At final follow-up, success rate was 100% (5 eyes complete, 6 eyes qualified) in the OAGV group compared to 31% (0 eyes complete, 5 eyes qualified) in the CAGV group. One and two-year survival rates were 100% for OAGV compared to 62 and 38% for CAGV. Postoperative IOP was significantly lower at 1-month and final follow-up (p = 0.02) as was the number of glaucoma medications at 3, 6, 12-months and final follow-up (p < 0.05) in the OAGV group. CONCLUSIONS: Ologen-augmentation increased the success and survival rates of AGVs in childhood glaucomas. Further, Ologen mitigated the hypertensive phase and decreased medication dependency. Longer follow-up with a greater number of eyes is required to fully evaluate the effectiveness of OAGV.

Surgical outcomes of Glaucoma associated with Axenfeld-Rieger syndrome.

BACKGROUND: The surgical management of glaucoma associated with Axenfeld-Rieger Syndrome (ARS) is poorly described in the literature. The goal of this study is to compare the effectiveness of various glaucoma surgeries on intraocular pressure (IOP) management in ARS. METHODS: Retrospective cohort study at a university hospital-based practice of patients diagnosed with ARS between 1973 and 2018. Exclusion criterion was follow-up less than 1 year. The number of eyes with glaucoma (IOP ≥ 21 mmHg with corneal edema, Haabs striae, optic nerve cupping or buphthalmos) requiring surgery was determined. The success and survival rates of goniotomy, trabeculotomy±trabeculectomy (no antifibrotics), cycloablation, trabeculectomy with anti-fibrotics, and glaucoma drainage device placement were assessed. Success was defined as IOP of 5-20 mmHg and no additional IOP-lowering surgery or visually devastating complications. Kaplan-Meier survival curves and the Wilcoxon test were used for statistical analysis. RESULTS: In 32 patients identified with ARS (median age at presentation 6.9 years, 0-58.7 years; median follow-up 5.4 years, 1.1-43.7 years), 23 (71.9%) patients were diagnosed with glaucoma at median age 6.3 years (0-57.9 years). In glaucomatous eyes (46 eyes), mean IOP at presentation was 21.8 ± 9.3 mmHg (median 20 mmHg, 4-45 mmHg) on 1.0 ± 1.6 glaucoma medications. Thirty-one eyes of 18 patients required glaucoma surgery with 2.2 ± 1.2 IOP-lowering surgeries per eye. Goniotomy (6 eyes) showed 43% success with 4.3 ± 3.9 years of IOP control. Trabeculotomy±trabeculectomy (6 eyes) had 17% success rate with 14.8 ± 12.7 years of IOP control. Trabeculectomy with anti-fibrotics (14 eyes) showed 57% success with 16.5 ± 13.5 years of IOP control. Ahmed© (FP7 or FP8) valve placement (8 eyes) had 25% success rate with 1.7 ± 1.9 years of IOP control. Baerveldt© (250 or 350) device placement (8 eyes) showed 70% success with 1.9 ± 2.3 years of IOP control. Cycloablation (4 eyes) had 33% success rate with 2.7 ± 3.5 years of IOP control. At final follow-up, mean IOP (12.6 ± 3.8 mmHg, median 11.8 mmHg, 7-19 mmHg) in glaucomatous eyes was significantly decreased (p < 0.0001), but there was no difference in number of glaucoma medications (1.6 ± 1.5, p = 0.1). CONCLUSIONS: In our series, greater than 70% of patients with ARS have secondary glaucoma that often requires multiple surgeries. Trabeculectomy with anti-fibrotics and Baerveldt glaucoma drainage devices showed the greatest success in obtaining IOP control.

Visual field fluctuations correlating with the menstrual cycle in a patient with optic pathway glioma.

Optic pathway gliomas are commonly associated with vision loss in children. We describe an 18-year-old woman with neurofibromatosis, type 1 and an optic nerve glioma who showed reproducible visual field defects that worsened midmenstrual cycle and returned to baseline during menses. To our knowledge, this is the first reported case of visual field fluctuations in a patient with an optic nerve glioma that correlated with her menstrual cycle.

Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease.

Combined pituitary hormone deficiency (CPHD) is a genetically heterogeneous disorder caused by mutations in over 30 genes. The loss-of-function mutations in many of these genes, including orthodenticle homeobox 2 (OTX2), can present with a broad range of clinical symptoms, which provides a challenge for predicting phenotype from genotype. Another challenge in human genetics is functional evaluation of rare genetic variants that are predicted to be deleterious. Zebrafish are an excellent vertebrate model for evaluating gene function and disease pathogenesis, especially because large numbers of progeny can be obtained, overcoming the challenge of individual variation. To clarify the utility of zebrafish for the analysis of CPHD-related genes, we analyzed the effect of OTX2 loss of function in zebrafish. The otx2b gene is expressed in the developing hypothalamus, and otx2bhu3625/hu3625 fish exhibit multiple defects in the development of head structures and are not viable past 10 days post fertilization (dpf). Otx2bhu3625/hu3625 fish have a small hypothalamus and low expression of pituitary growth hormone and prolactin (prl). The gills of otx2bhu3625/hu3625 fish have weak sodium influx, consistent with the role of prolactin in osmoregulation. The otx2bhu3625/hu3625 eyes are microphthalmic with colobomas, which may underlie the inability of the mutant fish to find food. The small pituitary and eyes are associated with reduced cell proliferation and increased apoptosis evident at 3 and 5 dpf, respectively. These observations establish the zebrafish as a useful tool for the analysis of CPHD genes with variable and complex phenotypes.

Rate of Complete Catheterization of Schlemm's Canal and Trabeculotomy Success in Primary and Secondary Childhood Glaucomas.

PURPOSE: Despite the increasing use of microcatheters to perform 360-degree trabeculotomy, the rate of complete Schlemm's canalization in different forms of pediatric glaucoma is under-reported. DESIGN: Retrospective institutional observational case series. METHODS: Ocular diagnoses and surgical details of 60 pediatric patients (≤18 years old) who underwent trabeculotomy between 2013 and 2019 were collected. Surgical success was defined as an intraocular pressure (IOP) of 5-20 mm Hg and no additional IOP-lowering surgery. RESULTS: Eighty-five eyes of 60 patients underwent trabeculotomy. For bilateral cases, the first eye to undergo surgery was included for analysis. Diagnoses included primary congenital glaucoma (PCG n = 22), juvenile open angle glaucoma (JOAG n = 16), glaucoma following cataract surgery (GFCS n = 15), and other secondary forms of glaucoma (n = 7). Canalization using a microcatheter was attempted in 52 of 60 eyes (87%) of which 21 (40%) achieved full 360-degree. Complete canalization was attained in 69% of JOAG patients, which was significantly higher than in PCG patients (22%; P = 0.007), but not GFCS (36%) and other secondary glaucoma (29%). The 5-year survival rate for all eyes was 75% with 95% confidence interval (CI), 57 to 86. Survival curves for 360-degree catheter, 270-degree to 360-degree combined catheter/Harms trabeculotome, and <180-degree Harms trabeculotome trabeculotomies were significantly different (P < 0.001) with 5-year survival rates of 100%, 69% with 95% CI, 16 to 93, and 48% with 95% CI, 29 to 64, respectively. CONCLUSIONS: A 360-degree catheter trabeculotomy is highly effective in obtaining IOP control; however, complete canalization of Schlemm's canal is most frequently achieved in JOAG patients. Congenital anomalies or scarring from previous surgeries, which prevents full canalization, may inherently decrease success of angle surgery in other glaucoma.

Glaucoma and Cornea Surgery Outcomes in Peters Anomaly.

PURPOSE: To conduct a qualitative description of corneal and glaucoma outcomes in Peters anomaly. DESIGN: Retrospective case series. METHODS: Children with Peters anomaly who presented between 1982-2017 were included. Visual acuity, intraocular pressure (IOP), survival of corneal grafts, and success of glaucoma surgery (defined as IOP of 5-20 mm Hg and no additional IOP-lowering surgery or visually devastating complications) were analyzed. RESULTS: Fifty-eight eyes of 37 patients (19 males) with Peters anomaly presented at 0.7 ± 1.5 years of age and had a follow-up of 10.2 ± 10.8 years. Twenty-three eyes underwent penetrating keratoplasty (PKP) with an average of 2.0 ± 1.3 grafts per eye. PKP survival at 1 year was 60% (95% confidence interval 41-75%) but decreased at 10 years to 34% (95% confidence interval 18-51%). Thirty-four eyes were diagnosed with glaucoma at 2.8 ± 6.4 years of age. Twenty eyes required glaucoma surgery, and the average number of IOP-lowering surgeries was 2.9 ± 2.0 per eye. Glaucoma drainage devices (15 eyes) had a 53% success rate. Laser cycloablation (9 eyes, transcleral or endoscopic) had a success rate of 67% with 2.0 ± 1.0 treatments per eye. Trabeculectomy with mitomycin C (8 eyes) and trabeculotomy (8 eyes) had 25% and 0% success rates, respectively. Fifteen eyes that underwent glaucoma surgery obtained IOP control, and GDD with or without cycloablation accounted for 80% of the successes. Eyes that underwent PKP did not show increased rates of glaucoma, higher IOP, or a greater necessity for IOP-lowering surgery. CONCLUSIONS: In Peters anomaly, PKP shows poor long-term success. In addition, >50% of eyes with Peters anomaly have secondary glaucoma that often requires multiple surgeries.

Retinal detachment and infantile-onset glaucoma in Stickler syndrome associated with known and novel COL2A1 mutations.

BACKGROUND: Few reports on surgical outcomes after retinal detachment in Stickler syndrome exist. Also, infantile-onset glaucoma associated with Stickler syndrome has been rarely reported and no reports exist that examine outcomes after glaucoma surgery. This study describes the clinical and genetic associations and the long-term outcomes of retinal detachment repair or glaucoma surgery in patients with Stickler syndrome. MATERIALS AND METHODS: Retrospective, single-center, case series of patients with Stickler syndrome. Demographics, clinical features, genetic mutations, and long-term surgical outcomes of eyes that experienced retinal detachment or diagnosed with infantile-onset glaucoma were assessed. RESULTS: Fifteen patients were identified with a mean age of 13 years at presentation and followed for a mean of 6 years. Two-thirds were male. Genetic analysis was performed as part of routine examination in nine patients from eight families. All were identified as having variants in COL2A1, three of which were novel. Six eyes of six patients experienced retinal detachment. Fifty percent of eyes without prophylactic laser treatment experienced retinal detachment, whereas only 5% of eyes that underwent prophylactic therapy detached. Despite surgical intervention for retinal detachment, five eyes became phthisical. Five eyes of three patients were diagnosed with infantile-onset glaucoma. All five eyes required multiple glaucoma surgeries, and three eyes became phthisical. CONCLUSIONS: This study illustrates the surgical challenges encountered in patients with Stickler syndrome. Additionally, infantile-onset glaucoma may be more prevalent than previously reported and presents a challenge in terms of management. A multidisciplinary approach is recommended to provide optimal care to these patients.

Retinoic Acid Maintains Function of Neural Crest-Derived Ocular and Craniofacial Structures in Adult Zebrafish.

Purpose: Retinoic acid (RA) is required for embryonic formation of the anterior segment of the eye and craniofacial structures. The present study further investigated the role of RA in maintaining the function of these neural crest-derived structures in adult zebrafish. Methods: Morphology and histology were analyzed by using live imaging, methylacrylate sections, and TUNEL assay. Functional analysis of vision and aqueous humor outflow were assayed with real-time imaging. Results: Both decreased and increased RA signaling altered craniofacial and ocular structures in adult zebrafish. Exogenous treatment with all-trans RA for 5 days resulted in a prognathic jaw, while inhibition of endogenous RA synthesis through treatment with 4-diethylaminobenzaldehyde (DEAB) decreased head height. In adult eyes, RA activity was localized to the retinal pigment epithelium, photoreceptors, outer plexiform layer, inner plexiform layer, iris stroma, and ventral canalicular network. Exogenous RA increased apoptosis in the iris stroma and canalicular network in the ventral iridocorneal angle, resulting in the loss of these structures and decreased aqueous outflow. DEAB, which decreased RA activity throughout the eye, induced widespread apoptosis, resulting in corneal edema, cataracts, retinal atrophy, and loss of iridocorneal angle structures. DEAB-treated fish were blind with no optokinetic response and no aqueous outflow from the anterior chamber. Conclusions: Tight control of RA levels is required for normal structure and function of the adult anterior segment. These studies demonstrated that RA plays an important role in maintaining ocular and craniofacial structures in adult zebrafish.

Angle closure glaucoma in congenital ectropion uvea.

PURPOSE: Congenital ectropion uvea is a rare anomaly, which is associated with open, but dysplastic iridocorneal angles that cause childhood glaucoma. Herein, we present 3 cases of angle-closure glaucoma in children with congenital ectropion uvea. OBSERVATIONS: Three children were initially diagnosed with unilateral glaucoma secondary to congenital ectropion uvea at 7, 8 and 13 years of age. The three cases showed 360° of ectropion uvea and iris stromal atrophy in the affected eye. In one case, we have photographic documentation of progression to complete angle closure, which necessitated placement of a glaucoma drainage device 3 years after combined trabeculotomy and trabeculectomy. The 2 other cases, which presented as complete angle closure, also underwent glaucoma drainage device implantation. All three cases had early glaucoma drainage device encapsulation (within 4 months) and required additional surgery (cycloablation or trabeculectomy). CONCLUSIONS AND IMPORTANCE: Congenital ectropion uvea can be associated with angle-closure glaucoma, and placement of glaucoma drainage devices in all 3 of our cases showed early failure due to plate encapsulation. Glaucoma in congenital ectropion uvea requires attention to angle configuration and often requires multiple surgeries to obtain intraocular pressure control.