Calcified Sclero-Choroidal Choristomas in Mosaic RASopathies: A Description of a New Imaging Sign.

PURPOSE: To evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of patients with mosaic RASopathy. DESIGN: Single-center retrospective observational study. SUBJECTS: Ten eyes with calcified fundus lesions in 7 patients with mosaic RASopathy. METHODS: The lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT) scan where available. MAIN OUTCOME MEASURES: The imaging characteristics of calcified fundus lesions were assessed. RESULTS: We found 7 patients with mosaic RASopathies, 5 men and 2 women (3 with linear sebaceous nevus syndrome, 3 with oculoectodermal syndrome, and 1 with encephalocraniocutaneous lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but 2 of these lesions involved both the choroid and sclera, with 2 of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography, and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan, and all 4 showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, 1 had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. CONCLUSIONS: We propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retrospective evaluation of Postnatal Growth and Retinopathy of Prematurity (G-ROP) and Colorado Retinopathy of Prematurity (CO-ROP) screening algorithms in University of Pittsburgh Medical Centers cohort.

Of the 70,000 infants screened for retinopathy of prematurity (ROP) each year in the United States, only 43% develop any ROP, and <10% develop treatment-requiring ROP. Investigators have tried to develop new methods for determining more specific screening criteria, including the Postnatal Growth and Retinopathy of Prematurity (G-ROP) and Colorado Retinopathy of Prematurity (CO-ROP), to reduce the number of infants being screened while maintaining a high degree of sensitivity. We evaluated the records of 138 premature infants who received treatment for ROP between 2010 and 2021 with respect to G-ROP (129 infants) and CO-ROP (102 infants) to test the sensitivity of each. Using the G-ROP criteria, 0.8% (1/129) of treated infants had type 1 ROP that would have been missed and 3.1% (4/129) of total infants treated were missed. These infants would not have been screened or received treatment if G-ROP guidelines were followed. Using the CO-ROP criteria, 2% (2/102) of treated infants had type 1 ROP that would have been missed and 4.9% (5/102) of total infants treated were missed. In our study cohort, both sets of criteria proved less sensitive than our current screening guidelines.

Pediatric oral fluorescein angiography: a retrospective review from a single institution.

PURPOSE: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children. METHODS: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing. RESULTS: A total of 55 patients aged 3-18 with 79 examinations were included. No patient was excluded from the retrospective case review because of lack of recorded data. The main indications for oral FA included uveitis, retinal vasculopathy, disk pathology, and retinal lesions. Three children had transient side effects, and 1 had delayed urticaria 4 hours after examination. No child had anaphylaxis. One patient had suboptimal imaging due to nonadherence to the guidelines-recommended fasting protocol. All other examinations (78/79), where guidelines were followed, provided images adequate for clinical decision making. CONCLUSIONS: Based on our experience, we recommend that oral FA be considered, especially in children where intravenous access is less well tolerated while awake. Informed consent that includes the possibility of delayed side effects is advisable.

Thygeson's superficial punctate keratitis in children.

OBJECTIVE: To describe the first paediatric case series of Thygesons' superficial punctate keratitis (TSPK) with management outcomes. METHODS: A retrospective chart review was done for all children either diagnosed at initial presentation or referred with TSPK from 01/2012 to 08/2021 at a tertiary children's hospital. Records were assessed for signs, symptoms, diagnosis, steroid and cyclosporine 0.05% use. The main outcome measures were visual acuity, treatment response and total steroid exposure. RESULTS: Fifteen children (7 females), mean age at presentation 8 ± 4 years were included. All had bilateral disease and a BCVA of >20/40 in the better eye. All patients received topical fluorometholone 0.1%, (FML) initially. 80% had a good response to FML. Corneal scraping was done to exclude infectious causes in four cases due to poor initial response or clinical suspicion. All 4 needed EUA for scraping and anterior segment OCT, after which 2 had molecularly confirmed TGFBI-related stromal dystrophy. For the rest, slow steroid taper was done every 4-6 weeks and recurrences were treated by increasing steroid frequency. Cyclosporine 0.05% was started in nine patients (69%), 8 ± 6 months after initial presentation. The decrease in total steroid exposure per week after starting cyclosporine was statistically significant (p < 0.05). CONCLUSION: Children with TSPK respond quickly to steroids, however, recurrences are common, necessitating a slow taper. Non-response to steroid needs careful reconsideration of the diagnosis and may necessitate the use of an EUA. Using cyclosporine 0.05% reduces the total steroid exposure in TSPK.

Severe Familial Exudative Vitreoretinopathy, Congenital Hearing Loss, and Developmental Delay in a Child With Biallelic Variants in FZD4.

Importance: Familial exudative vitreoretinopathy (FEVR) is a nonsyndromic autosomal dominant retinal disorder commonly caused by variants in the FZD4 gene. This study investigates the potential role beyond ocular abnormalities for FZD4 gene variants in patients with FEVR. Objective: To evaluate the role of FZD4 in symptoms beyond those associated with FEVR through a patient with biallelic variants in FZD4. Design, Setting, and Participants: This case series included the DNA testing and phenotyping of 1 patient proband and her parents, combined with signaling assays, to determine the association of patient-derived compound heterozygous variants on FZD4 signaling and biologic function. Main Outcomes and Measures: FZD4 genes were tested using next-generation sequencing and Sanger sequencing. Cell-based assays measured the effect of the variants on FZD4 signaling. Results: The proband presented with absent red reflexes from complete tractional retinal detachments diagnosed at 3 days of age and failed the newborn screening hearing test. Auditory brainstem response at 6 months of age showed bilateral mild to moderate high-frequency sensorineural hearing loss. The patient manifested developmental delays in speech and walking. Intravenous fluorescein angiography (IVFA) of the patient's parents detected stage 1 FEVR. Genetic testing revealed 2 FZD4 variants in the patient, each variant found in 1 parent. Signaling assays confirmed that the presence of both variants was associated with significantly worse signaling activity compared with the heterozygous state. Conclusions and Relevance: Results of this case series suggest that extraocular syndromic FEVR was associated with FZD4 variants. The decrease in FZD4 signaling owing to the biallelic nature of the disease resulted in hearing deficits, developmental delays, and a more severe retinal phenotype.

Effect of Trainee Participation on Operative Times in Strabismus Surgery.

Introduction This study aimed to describe the difference in operative time during strabismus surgery in the presence and absence of a trainee with the operating physician. Methods This is a retrospective chart review of pediatric patients who underwent strabismus surgery by three surgeons from January 2016 through September 2019. Electronic medical records were reviewed and noted for operative times as well as the presence or absence of a trainee (postgraduate year [PGY]-3 ophthalmology resident, PGY-5 pediatric ophthalmology fellow, or both). Results The average time needed for a two-horizontal muscle recession by all the three surgeons in the absence of a trainee averaged at 35.7 minutes (range: 24-48). This is increased by 34% in the presence of a trainee with an average of 47.88 minutes (range: 20-81) with a p -value < 0.001. Similar comparisons were performed for a two-horizontal muscle recession in addition to bilateral inferior oblique weakening procedures for two surgeons. On average, in the absence of a trainee, this required an average of 61.9 minutes for completion with an increase of 31.8% with the participation of a trainee requiring 81.56 minutes. Discussion The presence of trainees, whether residents or fellows, is a crucial component of medical education and training. It is important for their learning and helps develop strong future surgeons. However, this may increase surgical procedure times and affect the efficiency of the primary surgeon. This has important implications for surgical scheduling, surgical time utilization, and surgical productivity of those involved in trainee education. Conclusion The presence of a trainee with a primary surgeon, although crucial to surgical training, may result in significant prolongation of strabismus surgical times.

Integrated Intraoperative Optical Coherence Tomography during Scleral Pass in Strabismus Surgery.

We describe a novel application of integrated intraoperative OCT (iiOCT) to strabismus surgery during the scleral pass and demonstrate it to be a useful tool. A number of complications can arise from inappropriate scleral pass depth during strabismus surgery, leading to an increased risk of unwanted complications including endophthalmitis, retinal detachment, and a lost or slipped muscle. Our study demonstrated that the use of iiOCT provides easy to interpret, real-time feedback to the strabismus surgeon and may translate to safer, more consistent scleral suturing during strabismus surgery and strabismus surgical training. .

Safety of apraclonidine eye drops in diagnosis of Horner syndrome in an outpatient pediatric ophthalmology clinic.

PURPOSE: To describe the efficacy and systemic side effects of apraclonidine drops 0.5% in children clinically suspected of having Horner syndrome. METHODS: The medical records of patients with clinically suspected Horner syndrome who underwent testing with apraclonidine 0.5% eyedrops were reviewed retrospectively. The following data were retrieved from the record: allergic reactions, somnolence, shallow respiration, pallor, or excessive fussiness noted by the examiner or parents. RESULTS: A total of 46 patients presenting with anisocoria and tested with apraclonidine 0.5% were included. Of these, 15 had a positive result, with reversal of anisocoria. The mean age of patients was 3.2 years (median, 0.91; mode, 0.25 years). Twenty-four patients were ≤1 year of age; 19 were ≤6 months. No systemic side effects were noted during the examination or reported by parents in any patients. CONCLUSIONS: The use of topical apraclonidine eyedrops has been described as an effective test for Horner syndrome. However, concerns have been raised regarding the potential systemic side effects in children, especially those under the age of 6 months. In our cohort, no systemic side effects were reported, including in those under 6 months of age.

Integrated Intraoperative Optical Coherence Tomography in Strabismus Surgery.

The advent of integrated intraoperative ocular coherence tomography (i2OCT) has opened the door for safer more complex surgeries of the retina and cornea. However, to limit its use to just two subspecialties within ophthalmology is an opportunity lost for many other subspecialties. Here, we describe the use of i2OCT in strabismus surgery. It can be used to identify extraocular muscles, especially in cases of strabismus reoperations, thereby augmenting the surgical technique. Its use to help train strabismus surgery is invaluable, allowing the trainee to understand the depth of the scleral pass during strabismus surgery. The authors describe these scenarios of training and augmenting the surgical technique.

Developing a pediatric ophthalmology telemedicine program in the COVID-19 crisis.

PURPOSE: To describe our methodology for implementing synchronous telemedicine during the 2019 novel coronavirus (COVID-19) pandemic. METHODS: A retrospective review of outpatient records at a single children's hospital from March 21 to April 10, 2020, was carried out to determine the outcome of already-scheduled face-to-face outpatient appointments. The week leading up to the March 21, all appointments in the study period were categorized as follows: (1) requiring an in-person visit, (2) face-to-face visit that could be postponed, and (3) consultation required but could be virtual. Teams of administrators, schedulers, and ophthalmic technicians used defined scripts and standardized emails to communicate results of categorization to patients. Flowcharts were devised to schedule and implement telemedicine visits. Informational videos were made accessible on social media to prepare patients for the telemedicine experience. Simultaneously our children's hospital launched a pediatric on-demand e-consult service, the data analytics of which could be used to determine how many visits were eye related. RESULTS: A total of 237 virtual ophthalmology consult visits were offered during the study period: 212 were scheduled, and 206 were completed, of which 43 were with new patients and 163 with returning patients. Following the initial virtual visit, another was required on average in 4 weeks by 21 patients; in-person follow-up was required for 170 patients on average 4.6 months after the initial virtual visit. None needed review within 72 hours. The pediatric on-demand service completed 290 visits, of which 25 had eye complaints. CONCLUSIONS: With proper materials, technology, and staffing, a telemedicine strategy based on three patient categories can be rapidly implemented to provide continued patient care during pandemic conditions. In our study cohort, the scheduled clinic e-visits had a low no-show rate (3%), and 8% of the on-demand virtual access for pediatric care was eye related.

Transposition of plicated horizontal muscles.

Various surgical techniques exist for simultaneous correction of a strabismus with both horizontal and vertical components. Transposition of horizontal muscles is most commonly performed on recessed and resected muscles. We describe a novel surgical technique that combines horizontal rectus muscle plication with a vertical transposition and present a small case series in which the technique was used to successfully correct both horizontal and vertical deviations.

Pre-, Intra-, and Post-Operative Evaluation of Extraocular Muscle Insertions Using Optical Coherence Tomography: A Comparison of Four Devices.

OCT (optical coherence tomography) is widely used in ophthalmology and pediatric ophthalmology, but limited research has been done on the use of OCT in strabismus. This study investigates the use of different OCT machines to image rectus muscle insertions pre-, intra-, and post-operatively in pediatric strabismus patients. The OCT machines used in the study were a Bioptigen (Leica Microsystems Inc., Buffalo Grove, IL, USA), Spectralis HRA+OCT with Anterior Segment Module (Heidelberg Engineering, Heidelberg, Germany), Visante (Carl Zeiss, Oberkochen, Germany), and Zeiss Rescan 700 (Carl Zeiss, Oberkochen, Germany). Measurements from the machines were compared with the caliper distance measured during the strabismus surgery before disinsertion or after reattachment. The OCT machines had moderate (Bioptigen: 0.62) to good intraclass correlation coefficients (Rescan: 0.83, Spectralis: 0.85, Visante: 0.88) with intra-operative measurements. To our knowledge, this is the first study to use an operating microscope with integrated intra-operative OCT to image rectus muscle insertions. OCT is a useful tool in strabismus surgical patients in the pre-, intra-, and post-operative settings, particularly in patients who have had previous surgery, when the muscle insertion is unknown. The ability to accurately image rectus muscle insertions has significant implications for the management of strabismus patients.

Ophthalmic Manifestations of Mycoplasma-Induced Rash and Mucositis.

PURPOSE: Mycoplasma pneumoniae is a common cause of pediatric respiratory infections, with a quarter having extrapulmonary complications, most commonly a mucocutaneous eruption involving the ocular surface. A detailed description of the ophthalmic manifestations in Mycoplasma-induced rash and mucositis (MIRM) is currently lacking in the scientific literature. METHODS: This is a retrospective chart review of consecutive cases of MIRM at a tertiary referral children's hospital between October 1 and December 1, 2018, with up to 2 months of follow-up. Main outcomes and measures were demographic information, clinical examination findings including visual acuity, detailed anterior segment findings, and course of both ophthalmic and systemic disease. RESULTS: Five patients were included. Age range was 8 to 17 years (mean age 11.9 years, median 11 years), with a strong male preponderance (4:1). All patients had inflammatory conjunctivitis. One patient had recurrent conjunctival pseudomembrane formation, whereas 2 patients had lid margin and conjunctival ulceration. No cases had corneal involvement and visual outcomes were excellent. CONCLUSIONS: MIRM is associated with ocular involvement in almost all cases. Although this is generally mild, conjunctival epithelial defects and pseudomembrane formation can occur. We recommend that pediatric ophthalmologists follow children who are hospitalized with MIRM as closely as they would those diagnosed with other mucocutaneous syndromes, such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Anterior Segment Optical Coherence Tomography of Previously Operated Extraocular Muscles.

BACKGROUND AND PURPOSE: To assess the possibility of determining the insertion distance from the limbus of previously operated extraocular rectus muscles (EOM) with the Heidelberg Spectralis anterior segment optical coherence tomography (AS-OCT). PATIENT AND METHOD: Subjects with a history of previous strabismus surgery underwent AS-OCT of the EOM before planned additional strabismus surgery. The EOM insertion distances from the limbus were measured pre-operatively on the AS-OCT and compared to the caliper distance measured during the strabismus surgery. RESULTS: Ten previously operated muscles on nine subjects underwent AS-OCT before subsequent additional strabismus surgery. Four additional un-operated muscles subsequently operated on, were also imaged with the AS-OCT pre-operatively. Subject ages ranged from 13-52 years old (mean ± SD; 27.9 ± 13.2). The muscle insertion could be definitely identified in 6/10 muscles previously operated and 4/4 un-operated muscles. The difference between the two measurements of limbus to insertion in previously operated muscles was ≤1mm in 3/6, and ≤1.5mm in 6/6; <1mm in 4/4 un-operated muscles. Of the four insertions not readily identifiable, two revealed the presence of the muscle with scar tissue; the other two, the muscle insertions, were not visible, which showed that the muscle was at least a minimal amount from the limbus. CONCLUSION: Our study showed that the Heidelberg AS-OCT is capable of imaging previously operated EOM, which can give valuable information to the strabismus surgeon. The information from the AS-OCT was useful in all cases. The insertion to limbus measurements between pre-operative and intra-operative were within 1.5mm in all of the cases that the muscle insertion was able to be identified. The ability to accurately image EOM insertions has significant implications for the pre-operative procedure planning in previously operated and complicated strabismus patients.

Anterior Segment Optical Coherence Tomography of the Horizontal and Vertical Extraocular Muscles With Measurement of the Insertion to Limbus Distance.

PURPOSE: To assess the possibility of determining the insertion distance from the limbus of horizontal and vertical extraocular rectus muscles with anterior segment optical coherence tomography (AS-OCT). METHODS: The right eyes of 46 patients underwent AS-OCT. The horizontal and vertical extraocular rectus muscle insertion distances from the limbus were measured in a masked fashion by two pediatric ophthalmologists. RESULTS: Forty-two lateral rectus, 43 medial rectus, 35 inferior rectus, and 40 superior rectus muscles of the right eyes of 46 patients were included. Insertion to limbus measurements (mean ± SD) were as follows: lateral rectus = mean 6.8 ± 0.7 mm, range = 4.8 to 8.4 mm; medial rectus = mean 5.7 ± 0.8 mm, range = 4.3 to 7.8 mm; inferior rectus = mean 6.0 ± 0.6 mm, range = 4.8 to 7.0 mm; superior rectus = mean 6.8 ± 0.6 mm, range = 5.5 to 8.1 mm. The intraobserver and interobserver correlation coefficients for the insertion to limbus measurements of all four rectus muscles exceeded 0.75 (excellent correlation). CONCLUSIONS: The study showed that AS-OCT is capable of imaging all four of the rectus muscle insertions and measuring the insertion to limbus distance, and is the second AS-OCT study to image the superior and inferior rectus muscle insertions. The insertion to limbus measurements between examiners and on repeat measurements were consistent and reproducible. The ability to accurately image extraocular rectus muscle insertions may have future implications for the preoperative procedure planning in patients who have had previous surgery. [J Pediatr Ophthalmol Strabismus. 2016;53(3):141-145.].

Hypertropia in unilateral isolated abducens palsy.

PURPOSE: To evaluate the incidence and features of hypertropia in abducens nerve palsy. METHODS: The records of consecutive patients with unilateral, isolated, previously unoperated abducens nerve palsy were reviewed for binocular alignment on cover testing, Krimsky measurement, or Hess screen testing. Patients with associated cranial nerve palsy (including bilateral abducens palsies), orbital disease, myasthenia gravis, Horner syndrome, hemiplegia, cerebellar signs, arteritis, or previous strabismus surgery were excluded. Control subjects underwent complete examination to confirm normality. RESULTS: A total of 79 patients were included (40 males; mean age 49.2 years). Hypertropia in lateral or central gazes was present in 15 of 79 cases (19%) on alternate cover or Krimsky testing, in 32 of 56 cases (57%) on Hess screen testing, and absent in all 30 normal controls. Of cases with hypertropia, the mean of the greatest hypertropia in lateral or central gaze on was 5.0(Δ) ± 2.3(Δ) (standard deviation; range, 1(Δ)-8(Δ)) routine clinical examination, and 5.8(Δ) ± 4.2(Δ) (range, 2(Δ)-24(Δ)) on Hess screen testing. Of 39 cases with partial abducens palsy evaluated by Hess screen testing, the ipsilesional eye was hypertropic in 24 (61%) and hypotropic in 15 cases (39%). CONCLUSIONS: Small-angle hypertropia is common in isolated, unilateral abducens and does not imply existence of multiple cranial neuropathies or skew deviation.

Eyelid desmoplastic trichilemmoma: 2 case reports and review.

Desmoplastic trichilemmomas (DTs) are a rare variant of trichilemmomas first described in 1985. Since then, 11 cases involving the eyelid have been reported. Two cases of this study raise this total to 13. DTs are often clinically confused with basal cell carcinoma and must be proven by biopsy to obtain the correct diagnosis. These lesions are more commonly present in patients older than 50 years. Despite the fact that they are benign, they are often associated with basal cell carcinomas and as such should be managed carefully, requiring excisional biopsy with frozen borders or Mohs controlled margins.