Alternative Biologic Therapy in Children Failing Conventional TNFα Inhibitors for Refractory, Noninfectious, Chronic Anterior Uveitis.

PURPOSE: A significant number of children with noninfectious, chronic anterior uveitis (CAU) fail to respond to conventional therapy; however, successful alternative biologic treatments (ABT) have not been well described. This study aims to review the clinical and treatment characteristics of children with CAU who require ABT. DESIGN: Retrospective, nonrandomized clinical study. METHODS: Setting: Tertiary center. STUDY POPULATION: Children with noninfectious CAU. OBSERVATION PROCEDURES: Clinical characteristics, uveitis course, complications, and treatment were compared among patients treated with methotrexate (MTX) monotherapy, conventional TNFα inhibitors (cTNFi), and ABT for >3 months. MAIN OUTCOME MEASURE: Success of ABT (abatacept, tocilizumab, and/or golimumab) in children failing conventional treatment. RESULTS: Of the 52 children with CAU, 75% had juvenile idiopathic arthritis. CAU was controlled in 15 children receiving MTX monotherapy, 28 receiving cTNFi, and 9 receiving ABT (n = 1, abatacept; n = 3, tocilizumab; n = 5, golimumab). Patients in the ABT group had a greater number of total ocular complications per person before ABT than those in the control groups (3.4 vs 0.7 [MTX], P < .001, and 1.5 [cTNFi], P < .001, respectively). In all 9 children on ABT, treatment led to control of CAU and topical glucocorticoids tapered to ≤2 drops/d with no new ocular complications. CONCLUSIONS: In this study, alternative biologics (abatacept, golimumab, and tocilizumab) were useful for treating CAU in children who fail MTX and cTNFi therapy. Patients who were controlled on ABT had more disease activity, ocular complications, and anti-cTNFi neutralizing antibodies (before ABT) than those managed with conventional therapy. Larger studies are required to confirm these findings.

Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants.

Importance: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant. Objective: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP. Design, Setting, and Participants: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021. Interventions: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection. Main Outcomes and Measures: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels. Results: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50% or more from pretreatment levels in 40 of 66 infants (61%) at 2 weeks and 31 of 61 infants (51%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95% CI, -0.41 to 0.08) after injection. Conclusions and Relevance: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.

CHARGE syndrome without colobomas: Ophthalmic findings.

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients-clinically confirmed diagnosis with positive CHD7 mutation-seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion in this study was absence of any form of a coloboma in either eye. In our cohort, all patients had a positive CHD7 mutation, in addition to a clinical diagnosis. 19.4% (13/67) of CHARGE patients did not have a coloboma in either eye. 69.2% (9/13) had strabismus, 76.9% (10/13) had a refractive error that warranted refractive correction, 23.1% (3/13) had amblyopia, 38.5% (5/13) had nasolacrimal duct obstruction, 30.8% (4/13) had dry eye syndrome and exposure keratopathy, 15.4% (2/13) had ptosis, 15.4% (2/13) had blepharitis, 15.4% (2/13) had Cortical Visual Impairment, 7.7% (1/13) of patients had optic nerve drusen, 7.7% (1/13) had Marcus Gunn Jaw Winking, and 7.7% (1/13) with an eyelid nevus. There are numerous ophthalmic findings in individuals with CHARGE Syndrome without colobomas. No study to date has evaluated the ophthalmic findings in CHD7 positive CHARGE patients without colobomas. These findings need to be assessed and treated to ensure optimal vision in the CHARGE patient population. Absence of coloboma does not rule out a diagnosis of CHARGE syndrome, and if there is a clinical suspicion, clinical confirmation then genetic testing would be warranted.

Incidence and Etiology of Presumed Fourth Cranial Nerve Palsy: A Population-based Study.

PURPOSE: To determine the incidence of isolated, presumed fourth nerve palsy in a defined population, and to report the frequency of each cause. DESIGN: Retrospective, population-based case series. METHODS: A population-based database was used to identify all cases of isolated fourth nerve palsy in Olmsted County, Minnesota, USA diagnosed over a 15-year period (January 1, 1978 to December 31, 1992). The most likely etiology was determined by review of the entire medical record by 2 ophthalmologists. A priori definitions were applied for assigning cause. The incidence of fourth nerve palsy and the frequency of each etiology were calculated. Decade of life at presentation was recorded. RESULTS: Seventy-three patients (74 episodes, 70 [95%] unilateral) were identified. Mean age at presentation was 41.8 (range 3.3-81.6) years. The age- and sex-adjusted annual incidence rate was 5.73 per 100 000 per year (95% confidence interval [CI] 4.31-7.14). The most common etiology was presumed congenital (49%), followed by hypertension (18%) and trauma (18%). One patient (1%) had fourth nerve palsy owing to a known intracranial neoplasm. For 3 patients (4%) the cause of fourth nerve palsy was undetermined. The most common decade of presentation overall was the fourth decade, including for presumed congenital cases. CONCLUSIONS: In this population-based study, the majority of isolated fourth nerve palsies were presumed congenital, even though they presented throughout adulthood. Other etiologies such as hypertension and trauma were less frequent, and in no case was an isolated fourth nerve palsy the presenting sign of an intracranial tumor.

A comparison of Icare PRO and Tono-Pen XL tonometers in anesthetized children.

BACKGROUND: Tonometry in the anesthetized child, vital for evaluating known or suspected glaucoma, remains limited to tonometers capable of supine recording. The Icare PRO measures intraocular pressure (IOP) in the sitting or supine patient. The purpose of this study was to compare Icare PRO and Tono-Pen tonometry during examination under anesthesia in eyes of supine children with normal eyes and glaucoma and/or corneal pathology. METHODS: In this prospective study of children undergoing examination under anesthesia, IOP was recorded in both eyes with Icare PRO and Tono-Pen immediately after mask anesthesia induction, with instrument order randomized. RESULTS: A total of 100 eyes of 50 children (median age, 58 months) were included. IOP range was 6-50 mm Hg by Icare PRO and 6-53 mm Hg by Tono-Pen. Mean IOP measured by Tono-Pen (18.9 ± 7.5) was higher than that measured by Icare PRO (16.7 ± 7.1 mm Hg) by 2.2 mm Hg (P < 0.001). The presence of corneal edema was associated with IOP measurements higher by Tono-Pen than by Icare PRO (mean difference, 8.4 mm Hg). When eyes with corneal edema were excluded from analysis, there was no correlation between central corneal thickness and the difference in IOP between the two instruments. CONCLUSIONS: IOP in eyes of supine children under anesthesia measured approximately 2 mm Hg higher by Tono-Pen than Icare PRO and this difference was greater in eyes with frank corneal edema. Icare PRO may become a valuable tool for tonometry in supine infants and children, but a confirmatory test should be considered in eyes with corneal edema.

The effect of repeated measurements and the use of topical anesthetic on rebound tonometry values in children.

Measurement of intraocular pressure (IOP) in children is important in the management of pediatric glaucoma. Availability of the Icare rebound tonometer has greatly facilitated our ability to obtain awake IOP in infants and children, but little has been reported on either the effect of repeated sequential IOP measurements with Icare or the effect of topical anesthetic on subsequent Icare tonometry. This prospective study of 20 eyes of 10 cooperative children (12 normal eyes, 8 with suspected or known glaucoma) found that neither 8 sequential Icare measurements nor application of topical anesthetic produced a statistically or clinically signficant change in measured IOP by rebound tonometry.

Intraocular pressure in children: the effect of body position as assessed by Icare and Tono-Pen tonometers.

PURPOSE: To explore the effect of body position (sitting vs supine) on intraocular pressure (IOP) in children, as assessed by the Icare PRO and the Tono-Pen. DESIGN: Prospective clinical study. METHODS: Children with known or suspected glaucoma and those without glaucoma were recruited from the Duke Eye Center pediatric clinic. Subjects underwent tonometry in both eyes while upright (sitting), after instillation of topical anesthetic, with either the Icare PRO or the Tono-Pen first, and then the second instrument (order randomized). Goldmann applanation tonometry (GAT) was then performed by a clinician masked to the previous measurements. The subjects were then placed in the supine position for 5 minutes, and tonometry using the Icare PRO and the Tono-Pen was obtained, in the same order used when they were the sitting position. RESULTS: Enrolled were 47 children (94 eyes). Mean seated IOP for GAT, Icare PRO and Tono-Pen were 16.4 ± 4.2, 17.5 ± 3.5, and 18.0 ± 3.9 mm Hg, respectively. The mean supine IOP for the Icare PRO and Tono-Pen were 18.4 ± 4.5 and 18.8 ± 4.2 mm Hg, respectively. This rise was +0.9 ± 2.3 mm Hg for Icare PRO (P = 0.01) and +0.7 ± 1.8 mm Hg for Tono-Pen (P = 0.009), respectively. CONCLUSION: In children, Icare PRO tonometry correlates well with GAT in the sitting position, and with the Tono-Pen in both the sitting and supine positions. IOP rises when a child changes position from sitting to supine when measured by the Icare PRO or the Tono-Pen. However, the increase, which is less than 1 mm Hg, seems clinically insignificant and is unlikely to alter glaucoma management in children.

Anterior segment photography in pediatric eyes using the Lytro light field handheld noncontact camera.

PURPOSE: To compare anterior segment findings identified in young children using digital photographic images from the Lytro light field camera to those observed clinically. METHODS: This was a prospective study of children <9 years of age with an anterior segment abnormality. Clinically observed anterior segment examination findings for each child were recorded and several digital images of the anterior segment of each eye captured with the Lytro camera. The images were later reviewed by a masked examiner. Sensitivity of abnormal examination findings on Lytro imaging was calculated and compared to the clinical examination as the gold standard. RESULTS: A total of 157 eyes of 80 children (mean age, 4.4 years; range, 0.1-8.9) were included. Clinical examination revealed 206 anterior segment abnormalities altogether: lids/lashes (n = 21 eyes), conjunctiva/sclera (n = 28 eyes), cornea (n = 71 eyes), anterior chamber (n = 14 eyes), iris (n = 43 eyes), and lens (n = 29 eyes). Review of Lytro photographs of eyes with clinically diagnosed anterior segment abnormality correctly identified 133 of 206 (65%) of all abnormalities. Additionally, 185 abnormalities in 50 children were documented at examination under anesthesia. CONCLUSIONS: The Lytro camera was able to document most abnormal anterior segment findings in un-sedated young children. Its unique ability to allow focus change after image capture is a significant improvement on prior technology.

Mimickers of age-related macular degeneration.

In the Western World, the leading cause of irreversible blindness is Age- Related Macular Degeneration (ARMD). It can have significant visual impairment, and it is important that the practicing ophthalmologist is knowledgeable in the diagnosis and treatment of ARMD. Equally important is knowledge in the diagnosis of other disease entities that may mimic ARMD, as this may change the prognosis, treatment and visual outcome of patients. This article discusses those diseases that mimic ARMD and their distinguishing features.