Evaluation of Genotypic Antiviral Resistance Testing as an Alternative to Phenotypic Testing in a Patient with DOCK8 Deficiency and Severe HSV-1 Disease.

Antiviral resistance frequently complicates the treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we present the case of an adolescent boy with dedicator of cytokinesis 8 (DOCK8) deficiency, who experienced recurrent infections with resistant HSV-1. We used both phenotypic and genotypic methodologies to characterize the resistance profile of HSV-1 in the patient and conclude that genotypic testing outperformed phenotypic testing. We also present the first analysis of intrahost HSV-1 evolution in an immunocompromised patient. While HSV-1 can remain static in an immunocompetent individual for decades, the virus from this patient rapidly acquired genetic changes throughout its genome. Finally, we document a likely case of transmitted resistance in HSV-1 between the patient and his brother, who also has DOCK8 deficiency. This event demonstrates that resistant HSV-1 is transmissible among immunocompromised persons.

Pediatric refractive surgery.

PURPOSE OF REVIEW: Refractive surgery procedures have been performed on children since the early 1980s. This article will review this history as well as current thoughts on treating children with large refractive errors. RECENT FINDINGS: Pediatric refractive surgery has developed slowly as very few children fit the criteria for treatment. For this reason, practice patterns are varied and publications are rare. Publications in recent years have focused on intraocular procedures over laser refractive surgery. SUMMARY: Pediatric refractive surgery is an evolving field as surgeons try to find the best long-term treatments for these young patients.

Transplant related ocular surface disorders: Advanced techniques for ocular surface rehabilitation after ocular complications secondary to hematopoietic stem cell transplantation.

HSCT has been linked to the development of an assortment of ocular surface complications with the potential to lead to permanent visual impairment if left untreated or if not treated early in the course of disease. Strategies for therapy include maintenance of lubrication and tear preservation, prevention of evaporation, decreasing inflammation, and providing epithelial support. The ultimate aim of treatment is to prevent permanent ocular sequelae through prompt ophthalmology consultation and the use of advanced techniques for ocular surface rehabilitation. We describe several rehabilitation options of ocular surface complications occurring secondarily during the post-HSCT course.

Pediatric Refractive Surgery: A 2015 Perspective.

Pediatric refractive surgery is an emerging field that can allow visual development in children where convention treatments have failed. The select groups of children who are eligible for refractive surgery at this young age are facing a life-long struggle with poor vision and have few other options. This article will discuss the groups of children that can benefit from this treatment, the difficulties faced in translating an adult surgery to the pediatric population and the benefits from performing the procedures.

Childhood myopia: epidemiology, risk factors, and prevention.

Our understanding of the dynamic interaction between the eye's growth and its ability to adapt to maintain vision has shown that childhood myopia is a significant prediction of progressive myopia and the potentially severe ocular comorbidities associated with it. It is important for us to better understand this process and its risk factors in order to better develop a prevention and treatment strategy. This article will discuss the epidemiology, risk factors and current therapeutic regimens for reducing myopic progression.

Clinical outcomes in paediatric tubulointerstitial nephritis and uveitis syndrome (TINU).

PURPOSE: To evaluate the clinical presentation, course, and outcomes of uveitis in paediatric patients with tubulointerstitial nephritis and uveitis syndrome (TINU). METHODS: Multicentric Retrospective Cohort Study 110 patients ≤21 years of age diagnosed with TINU from 10 sites across the United States and Canada. Clinical diagnosis of TINU required uveitis diagnosed by an ophthalmologist, elevated serum creatinine (SCr) and elevated urine ß2-microglobulin (ß2M) or abnormal urinalysis. Renal biopsy and systemic illness were not mandatory. Univariate and multivariate analysis was performed to analyse risk factors and treatment modalities. RESULTS: Median age was 13 years (Range (5.9-18.4); 52% male); median follow-up, 1.6 years (IQR 0.98-4.02). Uveitis was symptomatic in 90%, with bilateral anterior uveitis in 94%. Ninety-two (84%) patients required immunomodulatory treatment (IMT). Methotrexate (n = 44) and mycophenolate mofetil (n = 39) were the first agents after oral corticosteroids. 45% required addition of biologic agents (Adalimumab [n = 33], Infliximab [n = 8]). Younger age (p = 0.018), male sex (p = 0.011), and higher uveitis grade at presentation (p = 0.031) were associated with greater IMT ( ≥ 2) requirement. 53% had uveitis recurrence compared to 16% with nephritis recurrence. At the most recent visit, nephritis was controlled in 90%, while uveitis in 74%. Four (4%) patients required glaucoma surgery. Nine (8%) patients had renal complications. CONCLUSIONS: Most patients with TINU require steroid-sparing IMT for control of uveitis, with nearly half requiring addition of biologic agents. Urinalysis, urine ß2M and SCr testing should be considered in children presenting with uveitis, especially when the disease is bilateral and anterior.

Dilute brimonidine to improve patient comfort and subconjunctival hemorrhage after LASIK.

PURPOSE: To investigate whether dilute brimonidine (0.025%) reduces patient discomfort, subconjunctival hemorrhage, and injection after LASIK without a significant increase in the rate of flap complications or surgical enhancements. METHODS: This randomized, double-blind, prospective study enrolled 180 patients (360 eyes) in a contralateral eye comparison of topical dilute brimonidine, naphazoline/pheniramine, or Systane Ultra (Alcon Laboratories, Inc., Fort Worth, TX) administered shortly before LASIK for any indication. Patients were evaluated for subconjunctival hemorrhage, injection, and flap dislocation 1 hour and 1 day postoperatively. Patient questionnaires measuring patient comfort and ocular symptoms were administered at these same follow-up visits. Patients were examined for 3 months to determine similar outcomes for standard indices of safety, predictability, efficacy, and enhancement rates. RESULTS: Scores of patient discomfort, subconjunctival hemorrhage, and injection were significantly lower in eyes treated with dilute brimonidine at the 1 hour and 1 day postoperative examinations. Refloats for mild-flap edge wrinkling were required in 3 brimonidine eyes (2.5%), 1 naphazoline/pheniramine eye (0.8%), and no control eyes, but this difference did not reach statistical significance (P = .18). There was no significant difference between eyes at 3 months in terms of visual acuity, refractive error, corrected distance visual acuity, or rate of enhancement. CONCLUSIONS: Use of dilute brimonidine before LASIK reduces subconjunctival hemorrhage and injection and improves patient comfort after surgery. Flap edge wrinkling requiring refloat may still be a complication with dilute brimonidine.

Prevalence of cerebrotendinous xanthomatosis among patients diagnosed with early-onset idiopathic bilateral cataracts: final analysis.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.

Evaluating the speed of visual recovery following thin-flap LASIK with a femtosecond laser.

PURPOSE: To investigate the speed of visual recovery following myopic thin-flap LASIK with a femtosecond laser. METHODS: This pilot study prospectively evaluated 20 eyes from 10 patients who underwent bilateral simultaneous LASIK with the Femto LDV Crystal Line femtosecond laser (Ziemer Ophthalmic Systems AG) used to create a circular flap of 9.0-mm diameter and 110-µm thickness followed by photoablation with the Allegretto Wave Eye-Q (WaveLight AG) excimer laser. Binocular and monocular uncorrected distance visual acuity (UDVA), monocular contrast sensitivity, and a patient questionnaire were evaluated during the first hours, 1 day, and 1 month postoperatively. RESULTS: For monocular UDVA, 100% of eyes were 20/40 at 1 hour and 100% were 20/25 at 4 hours. For binocular UDVA, all patients achieved 20/32 by 30 minutes and 20/20 by 4 hours. Low frequency contrast sensitivity returned to preoperative baseline by 1 hour (P=.73), and showed a statistically significant improvement over baseline by 4 hours (P=.01). High frequency monocular contrast sensitivity returned to preoperative baseline by 4 hours (P=.48), and showed a statistically significant improvement by 1 month (P=.04). At 2 and 4 hours, 50% and 100% of patients, respectively, indicated that they would feel comfortable driving. CONCLUSIONS: Visual recovery after thin-flap femtosecond LASIK is rapid, occurring within the first few hours after surgery.

Frosted branch angiitis presenting after a SARS-CoV-2 infection.

PURPOSE: To report a case of frosted branch angiitis presenting in a pediatric patient with unremarkable laboratory work-up apart from SARS-CoV-2 IgG antibodies. OBSERVATIONS: Less than four weeks after a SARS-CoV-2 infection, a 10 year-old female presented to the emergency department with severe headache and intermittent fevers. During her hospital admission, the ophthalmology service was consulted for blurry vision. Subsequent eye examination revealed frosted branch angiitis. The patient initially received intravenous corticosteroids but was escalated to plasmapheresis to achieve resolution of her symptoms. Outpatient maintenance therapy consisted of an oral Prednisone taper and Infliximab infusion. CONCLUSION AND IMPORTANCE: This case represents a unique ocular manifestation of COVID-19, as recent SARS-CoV-2 was the sole identifiable cause of the patient's frosted branch angiitis. Additionally, this patient required plasmapheresis to control disease progression.

Sleep Challenges and Interventions in Children With Visual Impairment.

PURPOSE: To examine sleep patterns in a large and heterogeneous group of children with visual impairment. METHODS: A cross-sectional survey of parents of children with visual impairment was offered via the National Federation of the Blind and the National Organization for Albinism and Hypopigmentation. RESULTS: Complete survey results were available for 72 participants, aged 1 to 16 years. Parents of 52 (72%) children reported that their child had cycles of good sleep and bad sleep, and 50 (69%) reported that their child's sleep patterns caused significant stress for them or their family. Scores on the Childhood Sleep Habits Questionnaire (CSHQ) increased (> 41) in 64 (89%) children, indicating a likely clinically significant sleep problem. When compared to normative data from children aged 4 to 10 years, children in the current sample scored higher (more sleep problems) on all eight subscales on the CSHQ. The presence of comorbid developmental delay was most strongly associated with sleep problems. Supplemental melatonin and improving daytime and nighttime schedules or routines were reported as the most helpful for sleep. Many families reported a need for further information regarding melatonin use as a supplement. CONCLUSIONS: A high proportion of children with visual impairment experience clinically meaningful sleep problems, regardless of degree of light perception or visual acuity. There is a strong need for increased awareness and screening for sleep problems in this population. Potential treatment modalities, including supplemental melatonin, should be discussed with families. [J Pediatr Ophthalmol & Strabismus. 2022;59(2):77-86.].

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.

Comprehensive Assessment of Quality of Life, Functioning, and Mental Health in Children With Juvenile Idiopathic Arthritis and Noninfectious Uveitis.

OBJECTIVE: Pediatric uveitis can lead to sight-threatening complications and can impact quality of life (QoL) and functioning. We aimed to examine health-related QoL, mental health, physical disability, vision-related functioning (VRF), and vision-related QoL in children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis (JIA-U), and other noninfectious uveitis. We hypothesized that there will be differences based on the presence of eye disease. METHODS: A multicenter cross-sectional study was conducted at four sites. Patients with JIA, JIA-U, or noninfectious uveitis were enrolled. Patients and parents completed the Pediatric Quality of Life Inventory (PedsQL; health-related QoL), the Revised Childhood Anxiety and Depression Scale (RCADS; anxiety/depression), the Childhood Health Assessment Questionnaire (C-HAQ; physical disability), and the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) (VRF/vision-related QoL). Clinical characteristics and patient-reported outcome measures were compared by diagnosis. RESULTS: Of 549 patients, 332 had JIA, 124 had JIA-U, and 93 had other uveitis diagnoses. Children with JIA-U had worse EYE-Q scores compared to those with JIA only. In children with uveitis, those with anterior uveitis (JIA-U and uveitis only) had less ocular complications, better EYE-Q scores, and worse C-HAQ and PedsQL physical summary scores compared to those with nonanterior disease. In children with anterior uveitis, those with JIA-U had worse PedsQL physical summary and C-HAQ scores than anterior uveitis only. Further, EYE-Q scores were worse in children with bilateral uveitis and more visual impairment. There were no differences in RCADS scores among groups. CONCLUSION: We provide a comprehensive outcome assessment of children with JIA, JIA-U, and other uveitis diagnoses. Differences in QoL and function were noted based on underlying disease. Our results support the addition of a vision-specific measure to better understand the impact of uveitis.

Assessing the Validity and Reliability of the Effects of Youngsters' Eyesight on Quality of Life Questionnaire Among Children With Uveitis.

OBJECTIVE: The Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) questionnaire measures vision-related functioning (VRF) and vision-related quality of life (VRQoL) in children with uveitis. Our aim was to revise the alpha version of the EYE-Q to refine VRF and VRQoL subscales and to assess the validity of the EYE-Q. METHODS: Children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis, and other noninfectious uveitis were enrolled. Patients and parents completed the EYE-Q, Pediatric Quality of Life Inventory (overall quality of life), and Childhood Health Assessment Questionnaire (physical functioning). The development site completed the alpha version of the EYE-Q, and the composite sites completed the beta version. We compared item-subscale correlations, internal consistency, and construct and discriminant validity among the different versions. RESULTS: Of the 644 patients enrolled, 61.6% completed the alpha version, and 38.4% the beta version of the EYE-Q. Mean ± SD patient age was 11.1 ± 4.2 years, and 70% were female. Fewer White patients (73.5%) completed the alpha version compared to the beta version (86.2%; P < 0.001). With the exception of patient-reported VRF, both versions had similar item-subscale correlations. Version comparisons on scale internal consistencies indicated significant differences for parent- and patient-reported VRF, but each scale had a Cronbach's α of >0.80 beta. When data were combined, the EYE-Q showed significant differences between JIA-only and uveitis patients on all parent and patient scores, except for patient-reported VRF. CONCLUSION: The EYE-Q appears to be a valid measure of VRF and VRQoL in pediatric uveitis. Our results suggest it may be used as an outcome measure in multicenter pediatric uveitis studies.

New-Onset Chronic Recurrent Multifocal Osteomyelitis in a Child With Chronic Uveitis.

Chronic recurrent multifocal osteomyelitis (CRMO) has rarely been associated with uveitis. The authors report a case of new CRMO in a 15-year-old boy with HLA-B27 positive chronic anterior uveitis controlled with methotrexate. This case highlights a potential association between chronic uveitis and CRMO. [J Pediatr Ophthalmol Strabismus. 2019;56:e38-e40.].

Visual Acuity and Ophthalmic Outcomes in the Year After Cataract Surgery Among Children Younger Than 13 Years.

Importance: Cataract is an important cause of visual impairment in children. Outcomes reported from a large clinical disease-specific registry can provide real-world estimates of visual outcomes and rates of adverse events in clinical practice. Objective: To describe visual acuity and refractive error outcomes, as well as rates of amblyopia, glaucoma, and additional eye surgery, during the first year after lensectomy in children. Design, Setting, and Participants: A prospective observational study was conducted from June 18, 2012, to July 8, 2015, at 61 pediatric eye care practices among 880 children younger than 13 years at the time of lensectomy in at least 1 eye with follow-up within 15 months after surgery. Statistical analysis was performed from December 12, 2016, to December 14, 2018. Exposures: Lensectomy with or without implantation of an intraocular lens. Main Outcomes and Measures: Visual acuity as well as rates of amblyopia, glaucoma, suspected glaucoma, and other intraocular surgery. Results: Among the 880 children (432 girls and 448 boys; mean [SD] age at annual follow-up, 4.9 [3.8] years) in the study, lens surgery was bilateral in 362 (41.1%; 95% CI, 37.9%-44.4%) children and unilateral in 518 (58.9%; 95% CI, 55.6%-62.1%). An intraocular lens was implanted in 654 of 1132 eyes (60.2%; 95% CI, 57.0%-63.4% [proportions reported for eye-level outcomes account for the potential correlation induced by enrolling both eyes of some individuals; for participants who received bilateral surgery, these numbers will differ from the quotient of the number of cases divided by the total sample size]). Amblyopia was identified in 449 children (51.0%; 95% CI, 47.7%-54.3%). In children age 3 years or older, mean visual acuity was 0.30 logMAR (about 20/40) in 153 bilateral pseudophakic eyes, 0.49 logMAR (about 20/63) in 141 unilateral pseudophakic eyes, 0.47 logMAR (about 20/63) in 21 bilateral aphakic eyes, and 0.61 logMAR (about 20/80) in 17 unilateral aphakic eyes. Mean visual acuity improved with older age at surgery in eyes with bilateral pseudophakia by 0.2 logMAR line (99% CI, 0.02-0.4; P = .005) and by 0.3 logMAR line (99% CI, 0.04-0.60; P = .004) in eyes with unilateral pseudophakia. A new diagnosis of glaucoma or suspected glaucoma was made in 67 of 1064 eyes that did not have glaucoma prior to lensectomy (5.9%; 95% CI, 4.6%-7.7%); 36 of 273 eyes with bilateral aphakia (13.2%; 95% CI, 9.0%-19.0%), 5 of 308 eyes with bilateral pseudophakia (1.5%; 95% CI, 0.6%-4.2%), 14 of 178 eyes with unilateral aphakia (7.9%; 95% CI, 4.7%-12.8%), and 12 of 305 eyes with unilateral pseudophakia (3.9%; 95% CI, 2.2%-6.8%). Additional intraocular surgery, most commonly vitrectomy or membranectomy to clear the visual axis, was performed in 189 of 1132 eyes (17.0%; 95% CI, 14.8%-19.6%). Conclusions and Relevance: Amblyopia was frequently observed during the first year after lensectomy in this cohort of children younger than 13 years. For children age 2 years or older at surgery visual acuity was typically less than normal for age and was worse with unilateral cataract. Management of visual axis obscuration was the most common complication requiring surgical intervention during the first year after surgery.

Current thoughts in pediatric refractive surgery.

The goal of this article is to review current literature regarding the emerging field of pediatric refractive surgery. This encompasses current thought in adult refractive surgery, published literature in pediatric refractive surgery, and future possibilities for refractive technology in the pediatric population. This study includes a comprehensive review of literature in the general refractive surgery, cornea, and pediatric literature.

Topical timolol for an iris hemangioma.

Extraocular infantile hemangiomas have been shown to respond to oral and topical beta blockers, while there is little literature regarding the management of intraocular infantile hemangiomas with beta blockers. This case report discusses the management of an iris hemangioma with topical timolol, a treatment previously unreported in the literature.

Pharmacokinetics and Safety of Travoprost 0.004% Ophthalmic Solution Preserved with Polyquad in Pediatric Patients with Glaucoma.

PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of travoprost 0.004% preserved with Polyquad® (TRAVATAN®) in pediatric patients with glaucoma or ocular hypertension. METHODS: This was a phase 1, open-label, multicenter clinical study of patients aged ≥2 months to <18 years. Patients received daily administration of travoprost 0.004% preserved with Polyquad in both eyes for 7 days. Plasma samples were collected 30 min before the final dose and at 10, 20, 40, and 80 min postdose. The main outcome measure was maximum concentration of travoprost free acid in plasma (Cmax). RESULTS: Included in the PK analysis were 24 patients (average age 9.6 ± 4.9 years). At least 1 sample with quantifiable levels of travoprost free acid was collected for 11 patients. The mean Cmax was 0.0471 ± 0.0105 ng/mL for patients aged 2 months to <3 years; 0.0258 ± 0.0128 ng/mL for ages 3 to <12 years; and 0.0109 ± 0.0005 ng/mL for ages 12 to <18 years. Travoprost was undetectable in samples collected predose from pediatric patients. Treatment-related adverse events (AEs) included hyperemia, eye pain, and eye pruritus (n = 1 each). There were no discontinuations or drug-related serious AEs. CONCLUSIONS: Travoprost free acid concentration in plasma was low in pediatric patients, detectable in only 11 of 24 patients. There was no accumulation of travoprost over the course of treatment. No clear relationship was observed between age/body surface area and Cmax. No increased risk was identified for the use of travoprost 0.004% preserved with Polyquad in patients <18 years of age.

Pediatric refractive surgery.

This article reviews current thoughts regarding pediatric refractive surgery. This encompasses current trends in adult refractive surgery, differences between adult and pediatric refractive surgery, and future possibilities for refractive technology for the pediatric population.