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.

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.

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.

Lens regeneration using endogenous stem cells with gain of visual function.

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

Lanosterol reverses protein aggregation in cataracts.

The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.

The relationship between education levels, lifestyle, and religion regarding the prevalence of myopia in Israel.

BACKGROUND: The ultra-Orthodox Jewish community has a unique lifestyle including minimal outdoor activity and intense, prolonged nearby work, beginning at a very young age. Their prevalence of myopia is extremely high. This paper provides a unique insight into the attitudes of this community towards myopia. METHODS: Ultra-Orthodox Jewish parents of children who came to the pediatric ophthalmology clinic in one tertiary care and two community centers in ultra-Orthodox-oriented cities were given a questionnaire. Demographic information, along with myopia prevalence in the family, was gathered. In addition, their attitudes and common knowledge regarding myopia were investigated. RESULTS: 161 questioners were collected, mostly completed by mothers (n = 110, 68%). The average number of children per family was 6 (range 1-16). In 148 families (92%) at least one of the parents has myopia. The average parent refraction was - 4.5 diopters (range - 0.5 to 15 diopters). Out of 935 children, 410 (44%) wore glasses. Twelve parents (7%) believe that myopia is a disease and 94 (58%) reported that they are concerned because their child wears glasses. Twenty-four (15%) believe that glasses are a sign of a high education level. Regarding treating myopia progression, 144 (89%) think that myopia progression should be treated, but only 36 (22%) are aware of the available treatments for it. CONCLUSION: This study examines an insular community with a very high incidence of myopia. In this community most parents think that myopia progression should be treated but most of them are unaware of the currently available treatments.

Inferior rectus displacement in heavy eye syndrome and sagging eye syndrome.

PURPOSE: To evaluate if there is a nasal displacement of the vertical rectus muscles in heavy eye syndrome (HES) and/or sagging eye syndrome (SES) compared with age-matched controls. METHODS: We reviewed the charts of all patients with the diagnosis of HES or SES who were seen at the University of California San Diego (UCSD) between the years 2008-2016 who underwent magnetic resonance imaging (MRI) of the brain and orbits. The control group included patients who had brain and orbital MRIs at UCSD in the absence of known pathology in the orbits or globes. Measurements were taken by 3 separate examiners for all groups. RESULTS: Twenty-four patients (16 with SES and 8 with HES) and 24 age-matched controls were retrospectively reviewed. The superior rectus (SR) of patients with HES and SES was more nasally displaced from the midline compared with that of age-matched controls (p = 0.04, p = 0.03, respectively). The inferior rectus (IR) of patients with HES but not with SES was more nasally displaced from the midline compared with that of age-matched controls (p = 0.04, p = 0.62, respectively). In all groups, the IR nasal displacement from the midline was approximately double compared with the SR. CONCLUSIONS: There is a significant nasal displacement of the SR in HES and SES and IR in HES. The observed IR nasal displacement in HES is a new finding and may explain the residual hypotropia and/or esotropia following surgical interventions for HES not involving the IR.

Diagnosis and management of allergic conjunctivitis in pediatric patients.

BACKGROUND: Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. OBJECTIVE: To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. METHODS: To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. RESULTS: A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. CONCLUSION: The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.

Chemodenervation of extraocular muscles with botulinum toxin in thyroid eye disease.

BACKGROUND: Thyroid eye disease (TED) presents a management dilemma for strabismologists due to the variability of its clinical course. Prisms may be prescribed to relieve diplopia in small deviations. Surgical intervention, on the other hand, should not be done until the active phase of the disease has subsided. We report our experience with chemodenervation utilizing botulinum toxin (BT) injection in the management of TED-related strabismus. METHODS: A retrospective chart review was done on twenty-two (22) consecutive patients receiving BT injections at the University of California, San Diego (UCSD) Thyroid Eye Center. All BT injections were administered by a single physician under electromyographic guidance. RESULTS: The clinical records of 22 patients (18 females) were reviewed. Seven patients (32 %) had a reduction of their deviation to a point where surgery was not required. In six patients (27 %), surgery was required but an improvement in ocular deviation was found, altering the original surgical plan. In four patients (18 %), the deviation continued to progress after BT injection. Success rates were higher if pre-treatment deviation was less than 20 prism diopters ((∆)). CONCLUSION: One third of the chemodenervation-treated patients avoided surgical intervention, with an additional 27 % (total of 40 % of those who needed surgery) having a reduced deviation prior to surgery. Using BT injection to extraocular muscles to treat diplopia in TED patients is most effective in preventing surgery in those patients with 20(∆) or less of deviation.

Solutions in pediatric cataracts.

PURPOSE OF REVIEW: Modern pediatric cataract surgical techniques combined with a greater understanding of the natural history of aphakia and pseudophakia have changed the approach to the surgery of pediatric cataracts. RECENT FINDINGS: Advanced surgical techniques, new pharmacologic options and long-term refractive planning have improved surgical success. SUMMARY: It is essential that the ophthalmic surgeon who cares for children with cataracts is aware of these issues.

Publication rates of registered strabismus trials from ClinicalTrials.gov.

Presently, little is known regarding the characteristics and publication rates of registered strabismus trials from ClinicalTrials.gov. We queried registered strabismus trials that were completed prior to January 1, 2021, from ClinicalTrials.gov. Publication of trials in peer-reviewed journals was confirmed using PubMed.gov, ClinicalTrials.gov, and Google Scholar. Of the 117 trials found, only 69 (59%) were published with a publication delay of nearly 2.5 years. Interventional trials were associated with publication status compared with observational trials. The low publication rates and significant publication delay indicate potential bias in information dissemination of completed strabismus trials.

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.

Delayed luminance and chromatic contrast sensitivity in infants with spontaneously regressed retinopathy of prematurity.

BACKGROUND: The current study assessed whether contrast sensitivity is affected in preterm infants with a history of spontaneously regressed retinopathy of prematurity (ROP, Stages 1-3). Specifically, we employed luminance (light/dark) and chromatic (red/green) stimuli, which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. METHODS: Contrast sensitivity (CS) was measured using forced-choice preferential looking testing in 21 infants with a history of ROP and 41 control preterm infants who were born prematurely but did not develop ROP, tested between 8 and 47 weeks (2-11 months) postterm age. Infants were presented with chromatic and luminance drifting sinusoidal gratings, which appeared randomly on the left or right side of the monitor in each trial. The contrast of the stimuli varied across trials and was defined in terms of root mean squared cone contrast for long- and medium-wavelength cones. RESULTS: Between 8 and 25 weeks postterm, ROP infants had significantly worse CS, and there was a trend for greater impairment for luminance than chromatic CS. This delay was not seen at older ages between 26 and 47 weeks postterm. CONCLUSIONS: These findings are consistent with the concept that early maturation of the M pathway is vulnerable to biological insult, as in the case of ROP, to a greater extent than in the P pathway.

Improvement in academic behaviors after successful treatment of convergence insufficiency.

PURPOSE: To determine whether treatment of symptomatic convergence insufficiency (CI) has an effect on Academic Behavior Survey (ABS) scores. METHODS: The ABS is a six-item survey developed by the Convergence Insufficiency Treatment Trial Group that quantifies the frequency of adverse school behaviors and parental concern about school performance on an ordinal scale from 0 (never) to 4 (always) with total scores ranging from 0 to 24. The ABS was administered at baseline and after 12 weeks of treatment to the parents of 218 children aged 9 to 17 years with symptomatic CI, who were enrolled in the Convergence Insufficiency Treatment Trial and randomized into (1) home-based pencil push-ups; (2) home-based computer vergence/accommodative therapy and pencil push-ups; (3) office-based vergence/accommodative therapy with home reinforcement; and (4) office-based placebo therapy with home reinforcement. Participants were classified as successful (n = 42), improved (n = 60), or non-responder (n = 116) at the completion of 12 weeks of treatment using a composite measure of the symptom score, nearpoint of convergence, and positive fusional vergence. Analysis of covariance methods were used to compare the mean change in ABS between response to treatment groups while controlling for the ABS score at baseline. RESULTS: The mean ABS score for the entire group at baseline was 12.85 (SD = 6.3). The mean ABS score decreased (improved) in those categorized as successful, improved, and non-responder by 4.0, 2.9, and 1.3 points, respectively. The improvement in the ABS score was significantly related to treatment outcome (p < 0.0001), with the ABS score being significantly lower (better) for children who were successful or improved after treatment as compared to children who were non-responders (p = 0.002 and 0.043, respectively). CONCLUSIONS: A successful or improved outcome after CI treatment was associated with a reduction in the frequency of adverse academic behaviors and parental concern associated with reading and school work as reported by parents.

Global Ophthalmology Practice Patterns during COVID-19 Pandemic and Lockdown.

AIM: To assess the impact of practice patterns amongst global ophthalmologists during severe acute respiratory syndrome Coronavirus 2 (SARS Cov2) causing Corona virus disease (COVID-19) and understand the various modifications made to address emergency surgeries and practice needs. METHODS: An online survey was sent to practicing ophthalmologists around the world through email, Whatsapp™ ListServ17.0™ (for pediatric ophthalmologists), WeChat™ (China) and ophthalmology associations (Indonesia, Philippines, Ireland). All queries were collected and categorized. Responses to the queries were given according to the recommendations by the Ophthalmology association. Practices ability to deal with the COVID were also classified according to country and type of access to PPE. Statistical analyses of the association between these data and queries, where appropriate were carried out. RESULTS: One thousand nine hundred sixteen ophthalmologists were invited to participate in a survey between April 10th and April 30th, 2020 of which 1207 responded, which is a response rate of approximately 63%. The majority of respondents were from India, Indonesia, China, Singapore and the USA. Our study indicates a precipitous drop in surgical procedures with 46% (n = 538) ophthalmologists ceased to operate on their patients and almost 40% (n = 486) were doing less than 25% of their original number of surgeries. The intent to resume elective surgeries was a consideration in 41% (n = 495) after an evaluation of the situation and in consultation with professional bodies. More than 2/3 of the respondents (n = 703) made it a priority to use and mandate their patients to practice physical distancing, wearing masks, and hand dis-infection for protection to limit the spread of infection. CONCLUSION: This global survey provides a real-world assessment of diverse practices that were in various forms of "shut down mode" and circumstances with varying capabilities to deal with COVID. It is unprecedented that the collective wisdom for a curtailment of practice has had an enormous immediate and far reaching implications on the livelihoods of ophthalmologists, their staff, and their families. Nevertheless, ophthalmologists and their staff remain resilient and have adapted to these changes pragmatically.