Congenital primary aphakia.

PURPOSE: To describe the natural history, management, and visual outcome in children with congenital primary aphakia (CPA). METHODS: This is a multicenter retrospective consecutive case series from five academic centers in England and North America. RESULTS: A total of 27 eyes of 14 patients were included (male:female, 1.7:1). Thirteen patients had bilateral CPA, and 1 patient had unilateral CPA. Mean age at diagnosis was 18 months (median, 21; range, 0.5-144). Of 11 patients who underwent genetic testing, 9 had FOXE3 pathogenic variants. In all patients, visual acuity at presentation was not better than fixing and following light. Typical findings included silvery appearance of the cornea with vascularization (96%), glaucoma (81%), iridocorneal adhesions (74%), optic nerve coloboma (55%), abnormal vitreous (33%), retinal detachment (30%), and aniridia with hypoplasia of ciliary body (19%). Surgical interventions in select patients included penetrating keratoplasty (PKP), glaucoma drainage device implantation, and cyclophotocoagulation (CPC). CONCLUSIONS: Eyes with corneal ectasia and a silvery appearance of the cornea with vascularization should alert the physician to the possibility of CPA. Glaucoma causes globe enlargement and may increase the risk of corneal perforation, but glaucoma is often refractory to medical treatment, and the threshold for surgical treatment should be low. PKP outcomes are very poor.

Transcriptome from opaque cornea of Fanconi anemia patient uncovers fibrosis and two connected players.

Congenital corneal opacities (CCO) are a group of blinding corneal disorders, where the underlying molecular mechanisms are poorly understood. Phenotyping through specialized imaging and histopathology analysis, together with assessment of key transcriptomic changes (including glycosaminoglycan metabolic enzymes) in cornea(s) with CCO from a case of Fanconi anemia is the approach taken in this study to identify causal mechanisms. Based on our findings, we propose a novel mechanism and two key players contributing to CCO.

Can Ophthalmologic Examination Predict Abducens Nerve Recovery After Endoscopic Skull Base Surgery?

OBJECTIVES: While abducens nerve palsy (ANP) is a known risk in the setting of some endoscopic endonasal skull base surgery (ESBS), frequency and prognosis of post-operative palsy remain unknown. Our goals were to determine the frequency and prognosis of ANP after high-risk ESBS, and identify factors associated with recovery. METHODS: Retrospective case series of all patients with pathology at highest risk for abducens nerve injury (pituitary adenoma, chordoma, meningioma, chondrosarcoma, cholesterol granuloma) generated a list of patients with abducens nerve palsy after ESBS performed from 2011-2016. A validated ophthalmologic clinical grading scale measuring lateral rectus duction from 0 to -5 (full motion to inability to reach midline) was measured at multiple time points to assess recovery of ANP. RESULTS: Of 655 patients who underwent ESBS with increased risk of abducens injury, 40 (6.1%) post-operative palsies were identified and 39 patients with dedicated examination at multiple time points were included in subsequent analysis. Complete resolution was noted in 25 patients (64%) within 12 months. While 19 of 23 (83%) with a partial palsy had complete resolution, only six of 16 (38%) with a complete palsy resolved entirely (P = .005; Fisher's exact test). All six patients with delayed onset of palsy resolved (P = .070; Fisher's exact test). Meningioma and chordoma had higher rates of both temporary and permanent post-operative ANP (P < .0001; Fisher's exact). CONCLUSIONS: The frequency of post-operative ANP following ESBS is low, even in high-risk tumors. While only a minority of complete abducens nerve palsies recover, patients with partial or delayed palsy post-operatively are likely to recover function without intervention. LEVEL OF EVIDENCE: IV Laryngoscope, 131:513-517, 2021.

The association between epiblepharon and obesity: an experience at tertiary care center in Western Pennsylvania/North America.

PURPOSE: Epiblepharon is a congenital eyelid anomaly that occurs most frequently in Asian children. Recent literature has identified an association between obesity and increased rates of epiblepharon among Asian children. The purpose of our study was to determine whether obesity was also associated with epiblepharon in a non-Asian population. METHODS: The medical records of all children with a diagnosis of epiblepharon seen in the oculoplastic clinic at a single institution over a 2-year period were reviewed and included all the Caucasian children with epiblepharon. The average body mass index was calculated for all patients with epiblepharon. The rate of obesity among these children was compared with the national rate of childhood obesity in the United States as defined by the Center for Disease Control and Prevention. RESULTS: Our study included 10 Caucasian children with epiblepharon. There were 8 girls and 2 boys. The rate of obesity among non-Asian children with epiblepharon was 40%, which is substantially higher than the average rate of obesity among children in the USA. One child was overweight. CONCLUSIONS: This study suggests an association between obesity and epiblepharon in non-Asian children. Obesity likely contributes to anatomic variations in the midface and eyelids that can lead to the development of epiblepharon. Given the rising rates of childhood obesity, it is important to be aware of its association with epiblepharon in ethnic populations other than Asian.

Occult Rosacea Diagnosed After Recurring Blepharoplasty Incision Inflammation.

We report an unusual case of a 58-year-old Caucasian female who developed intermittent eyelid erythema, edema, and wound thickening in the early postoperative period after bilateral upper eyelid blepharoplasty. These flares of inflammation sometimes appeared to respond to systemic antibiotics and steroid preparations and sometimes not. Because of concerns for possible mycobacterial infection, biopsy of the upper eyelid incision was performed and histopathology confirmed rosacea. Symptoms resolved with oral azithromycin. Our patient did not have a diagnosis of rosacea preoperatively. We believe that rosacea should be kept in mind in cases with either prolonged inflammation or recurrent inflammation in previously quiet eyelid incisions.

Iris anomalies and the incidence of ACTA2 mutation.

BACKGROUND: Central cysts of the iris pigment epithelium, or iris flocculi, are frequently reported in the literature in association with thoracic aortic aneurysm and dissection due to smooth muscle alpha-actin 2 (ACTA2) mutations. Children with ACTA2 mutations may also present with congenital mydriasis. We report our experience regarding the frequency of ACTA2 mutation in children with the above iris anomalies. METHODS: This is a retrospective, consecutive case series of all children presenting for iris flocculi or congenital mydriasis at a single tertiary centre from October 2012 to December 2016. RESULTS: 13 children with iris flocculi and 3 with congenital mydriasis presented during the study period. 10 children with iris flocculi completed genetic testing, and none were positive for ACTA2 mutation. All children with congenital mydriasis presented with a multisystem smooth muscle dysfunction syndrome; two of these three children tested positive for missense R179 ACTA2 mutations. CONCLUSIONS: In this series, ACTA2 mutation or copy number variation was not detected in children presenting for iris flocculi, whereas congenital mydriasis was associated with R179 mutation in both cases that tested positive for ACTA2 mutation. The case of congenital mydriasis without typical cardiac features of the R179 ACTA2 phenotype or intracranial vasculopathy was negative for ACTA2 mutation. While all children presenting with these iris anomalies should be offered a genetic evaluation, incidence data should inform genetic counselling, particularly in the absence of a family history of aneurysm or sudden death, or systemic signs of smooth muscle dysfunction.

Bilateral endoscopic optic nerve decompression in an infant with osteopetrosis.

Osteopetrosis is a rare disorder of bone remodeling characterized by defective resorption leading to excessive skeletal mass including optic canal. Compression of the optic nerve from the narrowed optic canal is the most common cause of vision loss in children with osteopetrosis. We report the case of a 6-month old girl with osteopetrosis who underwent bilateral optic canal decompression via endoscopic transcaruncular approach for progressive deterioration of visual function secondary to compressive optic neuropathy from narrowed optic canals. The patient showed improvement in visual function postoperatively.

Induced Tropia Test and Visual Acuity Testing in Nonverbal Children.

The objective of our study was to compare the Cardiff Acuity Card© test (CAC test) (Kay Pictures Ltd) with the induced tropia test (ITT) in nonverbal children for the detection of monocular vision deficit. This is a retrospective case note review of 34 nonverbal children, aged 12-48 months, attending the pediatric ophthalmology clinic at Children's Hospital of Pittsburgh of UPMC between October 2014 and January 2015. 30/34 were included for analysis. Binocular visual acuity and monocular visual acuity were tested at 50cm in 30 and 17 patients, respectively. At 100cm, binocular visual acuity and monocular visual acuity were tested in 16 and 11 patients, respectively. All 30 children had successful induced tropia testing; 21 had no fixation preference and 9 had a fixation preference. Of those that had no difference on monocular visual acuity, five had a fixation preference at 50cm and three at 100cm. Out of 21 that had no fixation preference, 3 had a monocular visual acuity difference, but of only one line. Our study suggests that to obtain as much information as possible without losing the interest or cooperation of the child, it may be more beneficial to perform the CAC test with both eyes open, followed by ITT, before attempting monocular visual acuity testing with the CAC test. Obtaining visual information using ITT was much more attainable compared to monocular CAC testing. The sensitivity using CAC test to find a visual acuity discrepancy is 40% using ITT as the standard, and the specificity is 63%. If one loses the interest of the child after the ITT, at least some information will have been gleaned rather than none about monocular visual behavior. This provides a more complete, attainable approach to gathering visual information.

Case series: Pyramidal cataracts, intact irides and nystagmus from three novel PAX6 mutations.

PURPOSE: To investigate the association between novel PAX6 mutations to bilateral anterior pyramidal congenital cataracts (APyC), complete and intact irides, and nystagmus. OBSERVATIONS: This is a retrospective observational case series in a multi-center setting with genetic testing. Three female patients were diagnosed with bilateral APyC, intact irides and nystagmus. Genetic testing identified the three patients had novel missense mutations in PAX6 - c.128C > T; p.Ser43Phe (S43F), c. 197T > A; p.Ile66Asn (I66N) and c.781C > G; p.Arg261Gly (R261G). CONCLUSIONS AND IMPORTANCE: This study demonstrates a novel phenotype of bilateral APyC, intact irides, and nystagmus in whom genetic testing for PAX6 identified novel missense mutations (S43F, I66N, R261G) in highly conserved DNA-binding domains. Implications of understanding why the iris is present in these cases is discussed.

Coenzyme Q10 in the Treatment of Corneal Edema in Kearns-Sayre: Is There an Application in Fuchs Endothelial Corneal Dystrophy?

PURPOSE: Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway. METHODS: A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea". RESULTS: There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation. CONCLUSIONS: The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.

Pediatric Glaucoma: Pharmacotherapeutic Options.

Childhood glaucoma is a major therapeutic challenge for pediatric ophthalmologists and glaucoma specialists worldwide. Management depends on the etiology and age at presentation. A variety of drugs are available for the control of intraocular pressure in children; however, none of these drugs have been licensed by the regulatory agencies for use in children. Furthermore, evidence gained from randomized controlled trials in the pediatric population is sparse, and little is known regarding the use of newer anti-glaucoma preparations. This evidence-based review aims to discuss the available pharmacotherapeutic options for glaucoma in children. Topical adrenoceptor blockers, topical and systemic carbonic anhydrase inhibitors, prostaglandin (PG) analogs, adrenoceptor agonists, parasympathomimetics, and combined preparations are available for use in children, but usually as an off-label indication. Therefore, it is important to recognize that serious side effects have been reported, even with topical drops, and measures to reduce systemic absorption should be taken. Most drugs have been shown to have comparable ocular hypotensive effects, with the lowest occurrence of systemic side effects with PG analogs. Whereas a newly introduced prostaglandin analog, tafluprost, and some other preservative-free preparations have shown promising results in adult glaucoma patients, no pediatric reports are available as yet. Future studies may describe their role in treating pediatric glaucoma. This review also shares some suggested treatment pathways for primary congenital glaucoma (PCG), juvenile open angle glaucoma (JOAG), developmental glaucoma, aphakic/pseudophakic glaucoma, and uveitic glaucoma.

Isolated Sagittal Synostosis in a Boy with Craniofrontonasal Dysplasia and a Novel EFNB1 Mutation.

Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that shows greater severity in females and is largely attributed to mutations in EFNB1. A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS. Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis. His mother also showed clinical features of CFNS, but less severe. Genetic tests uncovered a novel C to T mutation at nucleotide 466 (c.466C>T) in exon 1 of EFNB1 for both. To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.

Cataract surgery in children with congenital keratolenticular adhesion (Peters anomaly type 2).

PURPOSE: To report the visual and surgical outcomes after cataract surgery in children with keratolenticular adhesion (Peters anomaly type 2). METHODS: The medical records of consecutive patients with keratolenticular adhesion (KLA) with partial (iris defects)/complete aniridia were retrospectively reviewed. Cataract surgery (in-the-bag irrigation and aspiration) with or without intraocular lens implantation and with or without broad iridectomy was performed. The main outcome measures were postoperative visual acuity, complications, and progression of corneal opacity. RESULTS: The study included 4 eyes of 3 patients ranging in age from 3 months to 7 years. The mean age at cataract surgery was 37 months; the median, 24 months (range, 3-84 months). The mean follow-up was 3.3 years and median was 2 years (range, 2-6 years). Preoperative visual acuity ranged from fixing and following objects to 20/200. Only 1 patient had PAX6 mutation-confirmed aniridia. The other 2 patients had partial iris defects. All eyes improved in visual acuity ranging from counting fingers at 3 feet to 20/60. There was no progression of corneal opacity. There were no postoperative complications. CONCLUSIONS: Children with KLA with complete or partial iris defects with localized corneal opacity and cataract can achieve satisfactory visual outcomes by undergoing meticulous lensectomy with or without iridectomy.

Pediatric cataract: challenges and future directions.

Cataract is a significant cause of visual disability in the pediatric population worldwide and can significantly impact the neurobiological development of a child. Early diagnosis and prompt surgical intervention is critical to prevent irreversible amblyopia. Thorough ocular evaluation, including the onset, duration, and morphology of a cataract, is essential to determine the timing for surgical intervention. Detailed assessment of the general health of the child, preferably in conjunction with a pediatrician, is helpful to rule out any associated systemic condition. Although pediatric cataracts have a diverse etiology, with the majority being idiopathic, genetic counseling and molecular testing should be undertaken with the help of a genetic counselor and/or geneticist in cases of hereditary cataracts. Advancement in surgical techniques and methods of optical rehabilitation has substantially improved the functional and anatomic outcomes of pediatric cataract surgeries in recent years. However, the phenomenon of refractive growth and the process of emmetropization have continued to puzzle pediatric ophthalmologists and highlight the need for future prospective studies. Posterior capsule opacification and secondary glaucoma are still the major postoperative complications necessitating long-term surveillance in children undergoing cataract surgery early in life. Successful management of pediatric cataracts depends on individualized care and experienced teamwork. We reviewed the etiology, preoperative evaluation including biometry, choice of intraocular lens, surgical techniques, and recent developments in the field of childhood cataract.

Improved visual function with dietary intervention in a child with lipemia retinalis.

We present a 4.8-year-old female with grade 3 lipemia retinalis due to lipoprotein lipase deficiency, an abnormal electroretinogram, and bilateral decreased visual acuity. Strict dietary intervention resulted in reversal of lipemia retinalis, normalization of her electroretinogram, and improved visual acuity in both eyes.

Defining success in infant penetrating keratoplasty for developmental corneal opacities.

BACKGROUND AND PURPOSE: Neonatal corneal opacities (NCO) are one of the common causes of visual impairment in infants. We present the two infants with penetrating keratoplasty (PKP) for unilateral NCO with different visual and graft outcomes, and illustrate the importance of timing of surgery, importance of visual rehabilitation, and the lack of necessity of a clear graft to achieve reasonable visual function in infants with NCO. PATIENTS AND METHODS: Two infants with unilateral NCO (Peters anomaly) underwent PKP at age of 5.5 weeks (Case One) and 16 weeks (Case Two). Postoperative optical correction, amblyopia therapy, visual and graft outcomes were recorded. RESULTS: At the last follow-up (9.5 years in both the cases), Case One achieved a best-corrected visual acuity (BCVA) of 20/80 with -22 D of contact lens. The graft had a small clear zone centrally but otherwise was opacified to some extent. Case Two achieved a BCVA of 20/125 at 30 cms eccentrically with a clear graft. Case Two was uncooperative for amblyopia therapy and optical treatment. CONCLUSION: For a successful visual outcome in NCO, early PKP, aggressive amblyopia therapy, optical correction, and commitment from the parents for longterm follow-up and demanding treatment are required.