Teprotumumab for Thyroid Eye Disease-related Strabismus.

PURPOSE: To assess and quantify teprotumumab's effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility. METHODS: We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab. RESULTS: Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation (p < 0.001), without significant change in mean horizontal deviation (p = 0.75). Supraduction, abduction, adduction, and infraduction significantly improved in the more restricted eye (p < 0.01, p < 0.01, p = 0.04, and p = 0.01, respectively). Thirty-five percent of patients underwent strabismus surgery posttreatment, at an average 10 months after last infusion. CONCLUSIONS: Teprotumumab produced a statistically significant reduction in vertical but not horizontal strabismus angles in primary position at distance. Extraocular motility in all 4 ductions also improved. A substantial minority of patients still required strabismus surgery following teprotumumab.

The influence of orbital architecture on strabismus in craniosynostosis.

PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.

Teprotumumab-related Cutaneous Hypersensitivity Reactions.

The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous hypersensitivity reaction was also observed during the treatment course in all cases, between the second and fifth infusions. Teprotumumab-related cutaneous reactions suggest a possible immunogenic component of the monoclonal antibody and highlight the importance of close monitoring during treatment.

Prescribing patterns for paediatric hyperopia among paediatric eye care providers.

PURPOSE: To survey paediatric eye care providers to identify current patterns of prescribing for hyperopia. METHODS: Paediatric eye care providers were invited, via email, to participate in a survey to evaluate current age-based refractive error prescribing practices. Questions were designed to determine which factors may influence the survey participant's prescribing pattern (e.g., patient's age, magnitude of hyperopia, patient's symptoms, heterophoria and stereopsis) and if the providers were to prescribe, how much hyperopic correction would they prescribe (e.g., full or partial prescription). The response distributions by profession (optometry and ophthalmology) were compared using the Kolmogorov-Smirnov cumulative distribution function test. RESULTS: Responses were submitted by 738 participants regarding how they prescribe for their hyperopic patients. Most providers within each profession considered similar clinical factors when prescribing. The percentages of optometrists and ophthalmologists who reported considering the factor often differed significantly. Factors considered similarly by both optometrists and ophthalmologists were the presence of symptoms (98.0%, p = 0.14), presence of astigmatism and/or anisometropia (97.5%, p = 0.06) and the possibility of teasing (8.3%, p = 0.49). A wide range of prescribing was observed within each profession, with some providers reporting that they would prescribe for low levels of hyperopia while others reported that they would never prescribe. When prescribing for bilateral hyperopia in children with age-normal visual acuity and no manifest deviation or symptoms, the threshold for prescribing decreased with age for both professions, with ophthalmologists typically prescribing 1.5-2 D less than optometrists. The threshold for prescribing also decreased for both optometrists and ophthalmologists when children had associated clinical factors (e.g., esophoria or reduced near visual function). Optometrists and ophthalmologists most commonly prescribed based on cycloplegic refraction, although optometrists most commonly prescribed based on both the manifest and cycloplegic refraction for children ≥7 years. CONCLUSION: Prescribing patterns for paediatric hyperopia vary significantly among eye care providers.

Surgical and anesthetic influences of the oculocardiac reflex in adults and children during strabismus surgery.

One of the most common untoward occurrences during strabismus surgery at all ages is the oculocardiac reflex. Although typically easily treated, the sudden bradycardia or cardiac arrest may add a few gray hairs to ophthalmologists and anesthesiologists alike as it can be potentially fatal. This updated review of the literature and novel detailed treatment algorithm may prevent patient morbidity and mortality through proper recognition of at-risk patients and rapid treatment through proper communication between surgical and anesthesia physicians/providers.

The socioeconomic effect of COVID-19 on pediatric ophthalmologists: data from the first 12 months.

PURPOSE: To investigate the socioeconomic effect on pediatric ophthalmologists (POs) of the first year of the COVID-19 pandemic and to assess the association of practice type with financial impact. METHODS: An email follow-up survey of all AAPOS active members (POs) in April 2021, was used in conjunction with two prior surveys. The majority of US states were represented, and respondents were categorized as academic/university (AU), hospital employee (H), or one of three types of private practice: multispecialty ophthalmology practice (MSP), pediatric ophthalmology/strabismus group (PG), or solo practice (SP). RESULTS: The cumulative results during this one-year period revealed 1,533,203 examinations not performed, of which 498,291 were Medicaid. Over 65,000 surgeries were not performed. The average salary loss per PO was $57,188. The total loss of revenue for the pediatric ophthalmology sector was over $303,788,000. Practice groups making at least 75% of their prior year revenue were as follows: H, 81%; AU, 64%; MSP, 52%; PG, 50%; SP, 40%. Salary reduction in each group was as follows: H, 4.2%; AU, 15.4%; MSP, 17.2%; PG, 23.1%; SP, 40.9%. The average loss per practice was $290,151. More than 95% of private practice POs received funds from the Paycheck Protection Program. CONCLUSIONS: At the one-year mark of the pandemic, patient care had been severely disrupted, with subsequent financial consequences. Private practice providers (and especially solo practices) were disproportionally negatively affected.

Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome.

The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues.

Internal carotid artery aneurysm presenting as diplopia via telemedicine during COVID-19.

A patient presented with acute onset of double vision during the start of the COVID-19 pandemic when elective medical care was restricted. Initially declining an in-person evaluation, she was examined using a telehealth video visit, incorporating multiple technological modalities to ascertain ophthalmic examination elements. Her findings prompted emergent neuroimaging, revealing a giant internal carotid artery aneurysm, which was successfully embolized to prevent debilitating and possibly fatal intracranial haemorrhage. This case report illustrates the successful use of telemedicine and remote patient data acquisition to make a life-saving diagnosis.

As the worm turns: An infant with exotropia.

A two-year-old full-term boy with a history of an intermittent exotropia presented to the pediatric ophthalmology clinic for routine follow-up. He was found to have a stable sensorimotor examination however dilated funduscopic examination of the right eye was significant for a dim foveal reflex with a new discrete, white, elevated retinal lesion superotemporal to the fovea with surrounding subretinal exudates. An examination under anesthesia (EUA) was performed two days later that revealed a subretinal posterior pole granuloma with hyperfluorescence and late leakage from the lesion without telangiectatic vessels on fluorescein angiography. A repeat EUA one month later demonstrated an increase in surrounding subretinal and overlying intraretinal fluid. The patient was started on topical 1% prednisolone with a presumed diagnosis of Toxocara granuloma. At EUA, three months later, the subretinal and intraretinal fluid had resolved. The topical steroids were tapered, and the patient continues to be followed closely.

Thyroid-Associated Orbitopathy: Management and Treatment.

Thyroid-associated orbitopathy (TAO) is a leading cause of orbital and strabismus symptoms in adults. Over the last decade, new treatments have greatly changed available options to alleviate symptoms and improve outcomes. This article discusses the pathophysiology and natural disease course of TAO, including when to pursue urgent treatment and when to consider other diagnoses. This article highlights the interventions that may alter the disease course and offers a comprehensive review on evidence-based interventions for both supportive therapy and systemic agents. The surgical strategies and principles for the treatment of TAO are discussed, including indications for combined surgical interventions and varying surgical techniques.

Socioeconomics of retinopathy of prematurity screening and treatment in the United States.

BACKGROUND: Retinopathy of prematurity (ROP) screening, an integral part of pediatric ophthalmology, can be time consuming and resource intensive. The purpose of this study was to evaluate the economic landscape of ROP screening and treatment among pediatric ophthalmologists in the United States. METHODS: An online survey was distributed to US pediatric ophthalmologists through a pediatric ophthalmology email listserv. Survey results were compiled, and responses were deidentified and analyzed, with particular focus on factors affecting financial compensation. RESULTS: A total of 97 responses were collected. Almost half of respondents worked in private practice settings. Over 80% of respondents had a formal contract to perform ROP care, but only 26% enlisted the assistance of an attorney to negotiate their contract. Just over half of respondents believed themselves adequately compensated for their services. Respondents that had retained an attorney for contractual negotiations were more likely to have a higher mean annual compensation rate ($126,545 ± $145,133 vs $70,214 ± $50,671; P = 0.05). Physicians who believed themselves adequately compensated were more likely to be in academic practice settings (78% academic vs 55% combo/other vs 24% private; P < 0.001) and were more likely to have contracts to perform ROP care (68% with contracts vs 15% without; P = 0.001). Average annual compensation was $82,968 ± $84,132, approximately $24,000 higher than reported in 2013. CONCLUSIONS: More pediatric ophthalmologists among our respondents obtained contracts for their services, and compensation rates have increased since 2013. Nevertheless, concerns regarding under-compensation and time commitment persist, raising concerns about the long-term sustainability of current models for providing ROP services.

Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome.

BACKGROUND: Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. Excision repair cross-complementation group 6 (ERCC6 OMIM: *609413) is the gene most frequently mutated in CS. METHODS: A child with pre and postnatal growth failure and progressive neurologic deterioration with multisystem involvement, and with nondiagnostic whole-exome sequencing, was screened for causal variants with whole-genome sequencing (WGS). RESULTS: WGS identified biallelic ERCC6 variants, including a previously unreported intronic variant. Pathogenicity of these variants was established by demonstrating reduced levels of ERCC6 mRNA and protein expression, normal unscheduled DNA synthesis, and impaired recovery of RNA synthesis in patient fibroblasts following UV-irradiation. CONCLUSION: The study confirms the pathogenicity of a previously undescribed upstream intronic variant, highlighting the power of genome sequencing to identify noncoding variants. In addition, this report provides evidence for the utility of a combination approach of genome sequencing plus functional studies to provide diagnosis in a child for whom a lengthy diagnostic odyssey, including exome sequencing, was previously unrevealing.

Isolated bifid medial rectus muscle in adult-onset divergence insufficiency esotropia.

We present the case of a 77-year-old woman with adult-onset divergence insufficiency esotropia in which a bifid medial rectus muscle was identified intraoperatively. The patient had no past ocular, medical, syndromic, or traumatic history associated with this isolated horizontal rectus anomaly. Following identification of the bifid muscle, the original surgical plan was altered to asymmetric recession of the superior and inferior medical rectus heads.

Heavy eye syndrome: Myopia-induced strabismus.

Heavy eye syndrome is an important type of myopia-induced strabismus. We provide an overview of heavy eye syndrome, from its history to its most salient features. The theory of the orbital and rectus muscle pulley system as it relates to heavy eye syndrome and the prevailing theories on the pathophysiology of heavy eye syndrome in the current literature are discussed. We also highlight the presentation of heavy eye syndrome, its typical features on imaging, and differential diagnosis. Finally, we provide an overview on the management of heavy eye syndrome, including a description of several current surgical techniques.

The impact of the COVID-19 shutdown on US pediatric ophthalmologists.

In recent months, the COVID-19 pandemic has threatened the financial viability of pediatric ophthalmology practices. To measure the economic impact, the American Association of Pediatric Ophthalmology and Strabismus (AAPOS) Socio-economic Committee surveyed current US members at the peak of the COVID shutdown, in April 2020. With a robust response rate, the survey portrays that some pediatric ophthalmology practices are ominously strained, if not irreparably harmed.