Ocular Cicatricial Pemphigoid in Young Patients.

PURPOSE: The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. METHODS: Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. RESULTS: Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. CONCLUSIONS: OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

Biodegradable material for glaucoma drainage devices - A pilot study in rabbits.

PURPOSE: To study the morphological and histological characteristics of the fibrous capsule formed around a novel biodegradable glaucoma drainage device (GDD) implant made of oxidized regenerated cellulose (ORC) after 1 and 3 months of its implantation. METHODS: It was a prospective, interventional, preclinical experimental study using New Zealand white rabbits. All animals underwent GDD implantation with a novel biodegradable device. The device's body was made of ORC and attached to a silicone tube, connecting the body to the anterior chamber. Histopathology (hematoxylin and eosin/Masson's trichrome staining) and immunohistochemistry (Alpha-Smooth Muscle Actin expression) characteristics of the bleb formed around the novel device were noted at 1 and 3 months. RESULTS: One month post implantation, the biodegradable material produced a significant foreign body type of reaction evidenced by the exuberant infiltration by macrophages, lymphocytes, and multinucleated giant cells. The granulomatous response subsided by 3 months with disorganized collagen deposition on Masson's trichrome staining. The silicone tube was an internal control, and histopathology demonstrated well-organized collagen deposition around it at 3 months. Immunohistochemistry for α-smooth muscle actin also demonstrated more myofibroblast transformation at the site of the tube than the biodegradable implant. CONCLUSIONS: Our results indicate that the tissue response around a biodegradable GDD was different from the response to conventional devices. A diffuse, loose vascularized mesh was observed to develop, which may be more compatible with sustained IOP control over a longer period, in contrast to the usual thick and dense capsule formed around the non-biodegradable devices.

Efficacy of a novel low-cost torchlight transcorneal transillumination for diode laser transscleral cyclophotocoagulation in adult glaucoma.

PURPOSE: To study the outcomes of diode laser transscleral cyclophotocoagulation (TSCPC) with trans-corneal transillumination using a novel low-cost torchlight method in refractory glaucoma. METHODS AND ANALYSIS: This prospective interventional study included patients with refractory glaucoma who underwent TSCPC with trans-corneal transillumination (TSCPC-TI) using a novel low-cost torchlight method. Patients completing a minimum 6-month follow-up were analyzed. They were compared to a historical control group of patients who underwent TSCPC without transillumination (TSCPC-No TI) at 6-month follow-up period. We analyzed the mean laser energy delivered, post-laser intraocular pressure (IOP) reduction, number of antiglaucoma medications (AGM), the requirement of retreatment and complications of the procedure in both groups. RESULTS: 32 eyes of 29 patients comprised the TSCPC-TI group and were compared with 39 eyes of 37 patients in the TSCPC-No TI group. The TSCPC-TI group required lower energy than the TSCPC-No TI group (46.15 ± 22.8 Vs 80.65 ± 56.1 J p < 0.001). At 6-month follow-up, the TSCPC-TI group required lesser AGM for IOP control (2.33 ± 1.02 vs 3.02 ± 1.32 p = 0.01). There was a significantly reduced dependence of oral acetazolamide in the TSCPC-TI group at 6 months follow-up (15.6% vs 41% p = 0.03%). The success and response rates were 71.8% Vs 23.1%; p < 0.0001 and 87.5% Vs 51.2%; p = 0.001 significantly high in the TSCPC-TI group. The TSCPC-No TI group had a significantly high failure rate (12.5% Vs 48.2% p = 0.001). Hypotony (n = 1) and phthisis (n = 2) were noted TSCPC-No TI group. CONCLUSIONS: TSCPC with transillumination with a low-cost torchlight resulted in a more efficient and effective cycloablation than TSCPC without transillumination.

Efficacy of Ab Interno Revision for Trabeculectomy Bleb Failure using a Minimally Invasive Approach: A Prospective Study.

PRCIS: Ab interno bleb revision using the Grover and Fellman spatula offers potential benefits in improved intraocular pressure control and spare the conjunctiva for enhanced bleb management. PURPOSE: This study aimed to evaluate the safety and effectiveness of Ab-Interno Bleb Revision (AIBR) for treating failed trabeculectomy blebs. METHODS: This non-comparative case series enrolled glaucoma patients with failed trabeculectomy blebs, who underwent AIBR and were followed up for one year. Eligible patients received subconjunctival Mitomycin C 0.1 mL of 0.2 mg/mL (20 µg) five days before the AIBR, performed using the Grover and Fellman spatula. The primary outcome measures were intraocular pressure (IOP) and the usage of IOP-lowering medications one year after the procedure. Secondary outcomes included the procedure's failure rate and complications. Complete success was defined as achieving an IOP between 5-21 mmHg without medication, while qualified success required additional medical treatment. RESULTS: The study comprised 23 eyes from 23 patients, having a mean age of 59.66±14.93 years. Preoperatively, the mean IOP was 23.54±10.7 mmHg, and the mean anti-glaucoma medication requirement was 3.99±0.65, both significantly reduced to 15.7±6.9 mm Hg (P=0.009) and 1.26±1.2 (P <0.001) at one year, respectively. Overall, 19 eyes (82.6%) achieved success (Complete success: 39.2%, Qualified success: 43.4%), while in 4 (17.4%) patients the procedure failed (IOP >21 mmHg). 5 patients had transient hyphema, but there were no sight-threatening complications such as hypotony or choroidal detachment. CONCLUSION: Ab-Interno Bleb Revision (AIBR) is a safe, effective, and minimally invasive intervention for managing failed trabeculectomy blebs. By eliminating the need to reopen the conjunctiva, this technique offers a promising alternative for the treatment of this challenging condition.

Ophthalmologic profile of patients with systemic sclerosis.

PURPOSE: To study the ophthalmologic manifestations of systemic sclerosis (SSc) and its correlation with autoantibody profile. METHODS: A cross-sectional study on 200 eyes of 100 consecutive adult patients diagnosed with SSc was performed at a tertiary care center in Northern India. The examination of ocular adnexa, anterior segment, and posterior segment with slit-lamp biomicroscopy, tear film break-up time (TBUT), Schirmer's II test, and choroidal thickness measurement by swept-source ocular coherence tomography was done. Autoantibody profile was available for 85 patients, and its statistical association with the ocular examination findings was analyzed. RESULTS: In total, 100 patients (93 females and 7 males) were included. The mean age was 45.11 ± 11.68 years, and the mean disease duration was 6.93 ± 3.68 years. Meibomian gland disease was more commonly found in patients with the diffuse subtype of SSc (P = 0.037). Choroidal thickness was increased in 34% and decreased in 7% (reference range = 307 ± 79 mm) patients. Reduced TBUT, meibomian gland dysfunction, and eyelid stiffness had a statistically significant association with the presence of anti-Scl-70 antibody (P = 0.003, <0.0001, and 0.004, respectively). These patients had ocular fatigue, foreign body sensation, and burning sensation. No significant association was noted with the presence of SS-A/Ro and SS-B/La antibodies. CONCLUSION: This study highlights the need for an active comprehensive ophthalmic evaluation. Approximately 75% of the patients in our cohort had ocular involvement to varying extent. An isolated presence of anti-Scl70 antibody was also found to have a positive association with dry eye disease.

Correlation of anterior segment optical coherence tomography and ultrasound biomicroscopy in congenital corneal opacity.

PURPOSE: To investigate the correlation between swept-source anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in congenital corneal opacity (CCO). METHODS: All children with unilateral or bilateral congenital corneal opacities who underwent examination under anesthesia (EUA) and anterior segment optical coherence tomography (AS-OCT) imaging from January 1, 2022, to December 31, 2022, were included. Main outcome measures were corneal and anterior segment evaluation and correlation of UBM and AS-OCT findings. RESULTS: A total of 22 eyes of 15 patients were imaged using both technologies. The age at first EUA ranged from 11 days to 4 years. Different phenotypes were classified based on the clinical examination, UBM, and AS-OCT findings. Fourteen eyes were diagnosed with Peters anomaly, congenital corneal staphyloma was observed in 4 eyes, 2 eyes had coloboma, 1 eye had peripheral sclerocornea, and 1 eye was diagnosed with congenital primary aphakia. AS-OCT and UBM findings were closely correlated in 18 of 22 eyes (82%) but AS-OCT failed to provide detailed information in 4 eyes (18%) where UBM revealed more details. CONCLUSIONS: Although AS-OCT offers valuable preliminary data for initial assessment and counseling, it may not consistently provide precise assessments in all cases. Therefore, UBM should be considered for definitive evaluation.

Long-Term Efficacy of Selective Laser Trabeculoplasty in Primary Angle-Closure Disease After Laser Peripheral Iridotomy.

PURPOSE: To evaluate the long-term efficacy of selective laser trabeculoplasty (SLT) in eyes with primary angle-closure (PAC) and primary angle-closure glaucoma (PACG) following a laser peripheral iridotomy (LPI). METHOD: In this prospective cross-sectional study, 45 eyes of 34 patients with PAC/PACG diagnosis, uncontrolled intraocular pressure (IOP), and visible pigmented trabecular-meshwork (TM) at least 180° on gonioscopy following a LPI were recruited. Following a detailed baseline ophthalmic evaluation, all eligible eyes underwent SLT, and the patients were examined on day1, at 1 week, 1-, 3-, and 6-months, and 1-, 2-, 3-, 4-, and 5-year subsequently. The main outcomes measured were IOP, number of IOP-lowering agents, and complications. RESULTS: The mean age of the cohort was 57.80 ± 6.44 years, the male-female ratio was 8:26, and 17 eyes were PACG, and 28 were PAC. The baseline IOP was 23.81 ± 1.78 mm Hg, and was significantly declined at all follow-ups (p < .0001). The cumulative probability of overall success was 91% and 84% at 2-, and 5-year, respectively. At 5-year SLT provided drug-freedom in 80% of PAC and 23% of PACG eyes. Six eyes had IOP spike at 1-week and two patients underwent repeat SLT after 1-year. No other complications, such as pain/discomfort, inflammation, an increase in peripheral anterior synechiae and cystoid-macular-edema, were noted. CONCLUSIONS: SLT appears a safe and cost-effective procedure in PAC/mild- moderate PACG eyes with uncontrolled IOP after laser iridotomy. The long-term effectiveness of SLT as adjuvant treatment was good, but need large sized randomized studies for more validation.

Use of the Aurolab Aqueous Drainage Implant as a buckling element in pediatric retinal detachment with a preexisting glaucoma drainage device.

Purpose: To describe a novel technique for repair of rhegmatogenous retinal detachment in an eye with a previous non-valved glaucoma drainage device, the Aurolab Aqueous Drainage Implant (AADI). Observations: A 5-year-old child with bilateral primary congenital glaucoma presented with an inferior retinal detachment (RD) in the left eye. The left eye had a history of multiple surgical interventions including combined trabeculotomy and trabeculectomy done twice, AADI implantation and subsequently phacoaspiration with IOL implantation, 18 months prior to presentation. The left eye retinal detachment was managed by scleral buckling technique using the plate of the AADI as a buckling element without its explantation. Conclusions: AND IMPORTANCE: Management of retinal detachment in eyes with a pre-existing glaucoma drainage device (GDD) is uniquely challenging. Explantation of the GDD would likely result in intractable glaucoma post-operatively, requiring another surgery. Use of the trimmed plate of the GDD itself as the buckling element helped in settling the RD and preserving intraocular pressure control.

Diode Laser Transscleral Cyclophotocoagulation With a Novel Low-Cost Torchlight Method of Trans-Corneal Transillumination in Refractory Pediatric Glaucoma.

PRCIS: Trans-corneal transillumination (TI) aided transscleral cyclophotocoagulation (TSCPC) for intraocular pressure control of refractory pediatric glaucoma was found to be effective at 1 year. PURPOSE: To study 1-year outcomes of diode laser TSCPC with trans-corneal TI using a novel low-cost torchlight method in refractory pediatric glaucoma. METHODS: This prospective interventional study included children with refractory glaucoma who underwent TSCPC with the Oculight laser system (IRIS Medical Instruments) with trans-corneal TI (TSCPC-TI) using a novel low-cost torchlight method. Children completing a minimum 1-year follow-up were analyzed. They were compared with a historical control group of children who underwent TSCPC without TI (TSCPC-No-TI) at the 1-year follow-up period. We analyzed the mean laser energy delivered, post-laser intraocular pressure reduction, number of antiglaucoma medications (AGM), the requirement of retreatment and complications of the procedure in both groups. RESULTS: Forty-two eyes of 35 patients comprised the TSCPC-TI group and were compared with 31 eyes of 21 patients in the TSCPC-No-TI group. The TSCPC-TI group required lower energy than the TSCPC-No-TI group (24.7±7.8 J vs. 47.2±10.9 J, P <0.0001). Mean topical antiglaucoma drug requirement decreased from 2.9±0.08 before treatment to 0.66±0.8 at the end of 1 year in TSCPC-TI and from 2.6±1.0 before treatment to 0.6±0.77 in the TSCPC-No-TI groups, respectively ( P =0.15). There was a significantly reduced dependence of oral acetazolamide in the TSCPC-TI group at 1-year follow-up [5.7% vs. 61.9%, respectively ( P <0.001%)]. No adverse event of hypotony or choroidal detachment was noted in any group. CONCLUSIONS: TSCPC aided by TI with a low-cost torchlight for pediatric refractory glaucoma was found to be effective at 1 year in reducing intraocular pressure and the burden of medication.

Visual field indices in children and adults with comparable retinal nerve fiber layer thickness.

PURPOSE: To compare visual field indices in normal children and adults with similar retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT). METHODS: This cross-sectional study included 59 eyes of 59 normal children 6-18 years of age compared to normal adults. The children underwent visual field testing on the Humphrey Field Analyzer (HFA) and RNFL thickness measurement on OCT. Normal adults who had undergone OCT and visual field testing were retrieved from the OCT database. The mean deviation (MD) in each child was compared with the MD in RNFL thickness-matched eyes of normal adults. Children 6-11 years and 12-18 years were analyzed separately. RESULTS: Overall, the MD of children was significantly less than that of the normal adults despite having the same RNFL thickness (-2.42 ± 1.42 dB vs -1.61 ± 1.47 dB [P = 0.006]). When stratified by age, the difference in MD of children <12 years was significantly less than normal adults (-2.72 ± 1.5dB vs -1.53 ± 1.2 dB [P = 0.003) while in children >12 years, the difference did not reach statistical significance (-2.18 ± 1.2 vs -1.51 ± 1.32 [P = 0.12]). CONCLUSIONS: In our study cohort, children <12 years had lower visual field indices than adults. Their visual fields may appear worse than they would for an adult with the same RNFL thickness. Normal children >12 years of age seem to have a retinal sensitivity comparable to the adult normative database. It is worthwhile to consider the development of a separate pediatric normative database for the visual field assessment of children <12 years of age.

CYP1B1 and MYOC variants in neonatal-onset versus infantile-onset primary congenital glaucoma.

OBJECTIVE: To compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG). METHODS: This prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups. RESULTS: Babies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls. CONCLUSIONS: Patients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG.

Topical Steroid-Induced Cushing's Syndrome in a Newborn Following Goniotomy for Glaucoma.

Iatrogenic Cushing's syndrome is a life-threatening condition which requires an early diagnosis multidisciplinary approach. Despite reports of iatrogenic Cushing's syndrome following nasal or inhaled steroids, its development after topical betamethasone eye drops for a short duration is a less frequently reported or anticipated condition. We describe a 6-week-old infant who developed exogenous Cushing's syndrome following topical steroids after bilateral goniotomy for newborn glaucoma. The child was kept under observation and managed with a physiological dose of hydrocortisone. Parental counselling regarding the proper method of eye drop instillation and signs of steroid toxicity is of vital importance in all cases of pediatric ocular surgeries, especially where bilateral surgeries are undertaken.

Secondary developmental glaucoma.

The basic pathophysiology of all childhood glaucoma results from impaired outflow through the trabecular meshwork. Anterior Segment Dysgeneses (ASD) are a group of nonacquired anomalies associated with secondary developmental glaucoma, characterized by impaired development of the structures of the anterior segment. Many genes impact the development of the anterior segment. The cause of the development of the abnormalities is thought to be multifactorial. Molecular research has helped our understanding of the molecular basis of ASD and the developmental mechanisms underlying these conditions. Identifying the genetic changes underlying ASD has gradually led to the recognition that some of these conditions may be parts of a disease spectrum rather than isolated anomalies. The characterization of the underlying genetic abnormalities responsible for glaucoma is the first step toward developing diagnostic and screening tests, which could identify individuals at risk for disease before irreversible optic nerve damage occurs. It is also crucial for genetic counseling and risk stratification of later pregnancies. It also aids prenatal testing by various methods allowing for effective genetic counseling. This review summarizes various ocular and systemic conditions that result in secondary developmental glaucoma and provide an overview of the phenotypes, the diagnosis and principles of management of the various disorders.

Primary aphakia: clinical recognition is the key to diagnosis.

PURPOSE: To describe the presentation and treatment outcomes of a cohort of children with primary aphakia (PA). METHODS: Clinical photographs and ultrasound biomicroscopy (UBM) images of children presenting with sclerocornea and undetermined anterior segment dysgenesis between July 2017 and December 2020 were reviewed retrospectively. Children who had no crystalline lens visible on UBM were included. RESULTS: A total of 124 UBM images were captured for 124 children with cloudy corneas. Twelve children were identified with congenital primary aphakia: 5 had bilateral buphthalmos, 2 had buphthalmos in one eye and microphthalmos in the other, and 5 had bilateral sclerocornea-microphthalmia complex. All patients had a peculiar silvery-blue corneal appearance, with fine vascularization on the corneal surface. The overall corneal thickness was 409.1 ± 8.7 µm. The intraocular pressure (IOP) in eyes with glaucoma was 24.5 ± 7.3 mm Hg; in microphthalmic eyes, 11.4 ± 3.4 mm Hg (P <0.001). The raised IOP was treated with limited trans-scleral cyclophotocoagulation under transillumination and topical antiglaucoma medications. Children with glaucoma gained ambulatory vision with spectacles. CONCLUSIONS: Congenital primary aphakia has a characteristic clinical appearance and may present as buphthalmos or microphthalmos, depending on the extent of dysgenesis. Incisional surgery may result in phthisis because of ciliary body dysgenesis and unpredictable aqueous production.

Unilateral advanced glaucoma in isolated congenital ectropion uveae with ipsilateral ptosis: A pictorial description of five children.

Aim: To report the cases of five children with unilateral advanced glaucoma in isolated congenital ectropion uveae (CEU) with ipsilateral ptosis and myopia. Methods: This is an ambispective observational case series. After diagnosing one patient with CEU and glaucoma, consecutive patients presenting with unilateral ptosis, congenital iris anomaly, and glaucoma between 2014 to 2020, and had completed a minimum one-year postoperative follow-up, were analyzed. Results: Of the 1421 newly registered pediatric glaucoma patients in the period under review, five children were diagnosed with CEU. All patients presented with gradual painless diminution of vision in the left eye in early adolescence. The left eye of all patients had peculiar clinical features: mild congenital ptosis, high iris insertion, crypt-less smooth iris surface, congenital ectropion uveae, pigments over anterior lens capsule, high myopia, advanced glaucomatous optic disc cupping, and very high intraocular pressure (IOP), which was > 45 mmHg in all cases. The right eye showed signs of angle dysgenesis with mild anterior iris insertion and numerous fine iris processes. Antiglaucoma medications and angle surgery failed to control the IOP, and all children required glaucoma filtration surgery, resulting in reasonable IOP control. Despite the older age, postoperative strict amblyopia treatment resulted in significant improvement in vision. Conclusions: Although ectropion uveae and ptosis have been present since birth, unilaterality, and the asymptomatic nature of the disease led to the late presentation with irreversible damage. Early surgical management and amblyopia therapy are the cornerstones of management. Abbreviations: CEU = Congenital ectropion uvea, CIES = Congenital Iris Ectropion Syndrome, ASD = Anterior segment dysgenesis syndrome, BCVA = Best-corrected visual acuity, IOP = Intraocular pressure.

Anterior segment dysgenesis: Insights into the genetics and pathogenesis.

Childhood glaucoma is a treatable cause of blindness, provided it is recognized, diagnosed, and treated in time. WHO has estimated that it is responsible for Blind Years second only to cataracts. The fundamental pathophysiology of all childhood glaucoma is impaired outflow through the trabecular meshwork. Anterior segment Dysgeneses (ASD) are a group of non-acquired ocular anomalies associated with glaucoma, characterized by developmental abnormalities of the tissues of the anterior segment. The cause is multifactorial, and many genes are involved in the development of the anterior segment. Over the last decade, molecular and developmental genetic research has transformed our understanding of the molecular basis of ASD and the developmental mechanisms underlying these conditions. Identifying the genetic changes underlying ASD has gradually led to the recognition that some of these conditions may be parts of a disease spectrum. The characterization of genes responsible for glaucoma is the critical first step toward developing diagnostic and screening tests, which could identify individuals at risk for disease before irreversible optic nerve damage occurs. It is also crucial for genetic counseling and risk stratification of later pregnancies. It also aids pre-natal testing by various methods allowing for effective genetic counseling. This review will summarize the known genetic variants associated with phenotypes of ASD and the possible significance and utility of genetic testing in the clinic.

A modified model of glaucoma filtering surgery in Sprague-Dawley rats.

Animal models are useful in glaucoma research to study tissue response to wound healing. Smaller animals such as rats offer additional advantages in terms of availability of detection antibodies and microarrays with cheaper maintenance costs. In this study, we describe a glaucoma filtering surgery (GFS) model in adult Sprague-Dawley rats by performing a sclerostomy using a 26-G needle and additionally placing a silicone tube (27 G) connecting the anterior chamber to the subconjunctival space to maintain a patent fistula for the flow of aqueous humor, thus providing a more definitive bleb. This technique will be useful in identifying and modifying newer targets in the wound healing process in order to improve surgical outcomes following GFS.

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.