The Role of Insulin-like Growth Factor-1 and Its Receptor in the Eye: A Review and Implications for IGF-1R Inhibition.

PURPOSE: FDA approval of teprotumumab for thyroid eye disease in January 2020 reinforced interest in the pharmacologic potential of insulin-like growth factor-1 (IGF-1) and its receptor, IGF-1R. Despite recent approval and adaptation for ophthalmic use, IGF-1R inhibitors are not a new therapeutic class. In 1986, Yamashita described aIR3, a monoclonal antibody to IGF-1R (anti-IGF-1R), that inhibited the effect of IGF-1 on growth hormone release. Given the widespread presence of IGF-1R, interrupting this receptor can lead to systemic physiologic effects, some adverse. We aim to review what is known about IGF-1/IGF-1R in the eye and consider the possible local side effects, unintended consequences, and potential uses of this medication class. METHODS: A PubMed database search utilizing the keywords "insulin-like growth factor-1, eye, inhibitor, antibody, side effect" was performed to identify publications discussing IGF-1 in the human eye from January 2011 to August 2021. Criteria for acceptance included studies discussing human subjects or human tissue specifically related to the eye. RESULTS: Out of a total of 230 articles, 47 were organized in 3 subject groups for discussion: thyroid-associated orbitopathy, cornea and the ocular surface, and the retina and neovascularization. Review of the literature demonstrated that IGF-1 affects growth and development of the eye, epithelial proliferation, retinal angiogenesis, inflammation, and is associated with thyroid-associated orbitopathy. CONCLUSIONS: IGF-1R exists throughout in the human body, including the cornea, retina, and orbit. Research regarding ocular effects of IGF-1/IGF-1R outside thyroid eye disease is limited. Carefully designed studies and clinical assessments of patients undergoing treatment with anti-IGF-1R may identify ocular side effects and foster consideration of the role of anti-IGF-1R in ocular therapeutics. Given the increasing use of anti-IGF-1R antibodies, understanding their ocular effects, side effects, and potential systemic implications for use in disease is critical.

Firearm-associated ocular injuries: analysis of national trauma data / Lesões oculares relacionadas a armas de fogo: análise de dados nacionais de traumas nos EUA

ABSTRACT Purpose: The United States of America has the highest gun ownership rate of all high-income nations, and firearms have been identified as a leading cause of ocular trauma and visual impairment. The purpose of this study was to characterize firearm-associated ocular injury and identify at-risk groups. Methods: Patients admitted with firearm-associated ocular injury were identified from the National Trauma Data Bank (2008-2014) using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes and E-codes for external causes. Statistical analysis was performed using the SPSS 24 software. Significance was set at p<0.05. Results: Of the 235,254 patients, 8,715 (3.7%) admitted with firearm-associated trauma had ocular injuries. Mean (standard deviation) age was 33.8 (16.9) years. Most were males (85.7%), White (46.6%), and from the South (42.9%). Black patients comprised 35% of cases. Common injuries were orbital fractures (38.6%) and open globe injuries (34.7%). Frequent locations of injury were at home (43.8%) and on the street (21.4%). Black patients had the highest risk of experiencing assault (odds ratio [OR]: 9.0; 95% confidence interval [CI]: 8.02-10.11; p<0.001) and street location of injury (OR: 3.05; 95% CI: 2.74-3.39; p<0.001), while White patients had the highest risk of self-­inflicted injury (OR: 10.53; 95% CI: 9.39-11.81; p<0.001) and home location of injury (OR: 3.64; 95% CI: 3.33-3.98; p<0.001). There was a steadily increasing risk of self-inflicted injuries with age peaking in those >80 years (OR: 12.01; 95% CI: 7.49-19.23; p<0.001). Mean (standard deviation) Glasgow Coma Scale and injury severity scores were 10 (5.5) and 18.6 (13.0), respectively. Most injuries (53.1%) were classified as severe or very severe injury, 64.6% had traumatic brain injury, and mortality occurred in 16% of cases. Conclusion: Most firearm-associated ocular injuries occurred in young, male, White, and Southern patients. Blacks were disproportionally affected. Most firearm-associated ocular injuries were sight-­threatening and associated with traumatic brain injury. The majority survived, with potential long-term disabilities. The demographic differences identified in this study may represent potential targets for prevention.

RESUMO Objetivo: Os Estados Unidos têm a maior taxa de posse de armas de fogo de todos os países de alta renda e essas armas foram identificados como uma das maiores causas de trauma ocular e deficiência visual. O objetivo deste estudo foi caracterizar as lesões oculares associadas a armas de fogo e identificar grupos de risco. Métodos: Foram identificados pacientes hospitalizados com lesões oculares associadas a armas de fogo no período de 2008 a 2014, a partir do Banco de Dados Nacional de Trauma (National Trauma Data Bank), usando os códigos de diagnósticos da CID9MC e códigos "E" para causas externas. A análise estatística foi efetuada usando o programa SPSS. O nível de significância considerado foi de p<0,05. Resultados: De um total de 235.254 pacientes hospitalizados com trauma associado a armas de fogo, 8.715 (3,7%) tinham lesões oculares. A média de idade foi de 33,8 (DP 16,9) anos. A maioria foi de homens (85,7%), brancos (46,6%) e da região Sul (42,9%); 35% dos pacientes eram negros. As lesões mais comuns foram fraturas de órbita (38,6%) e lesões de globo aberto (34,7%). Os locais mais frequentes foram a residência (43,8%) e a rua (21,4%). Pacientes negros tiveram maior probabilidade de sofrer agressões (RP=9,0, IC 95%=8,02-10,11; p<0,001) e da ocorrência ser na rua (RP=3,05, IC 95%=2,74-3,39; p<0,001), enquanto pacientes brancos tiveram maior probabilidade de lesões autoprovocadas (RP=10,53, IC 95%=9,39-11,81; p<0,001) e da ocorrência ser na residência (RP=3,64, IC 95%=3,33-3,98; p<0,001). A probabilidade de lesões autoprovocadas aumentou com a idade de forma consistente, atingindo o máximo em pacientes com mais de 80 anos (RP=12,01, IC 95%=7,49-19,23; p<0,001). A pontuação média na escala de coma de Glasgow foi 10 (DP 5,5) e na escala de severidade da lesão foi 18,6 (DP 13,0). A maioria das lesões (53,1%) foi classificada como severa ou muito severa. Dentre os pacientes, 64,6% tiveram lesão cerebral traumática e 16% evoluíram a óbito. Conclusão: A maior parte das lesões oculares relacionadas a armas de fogo ocorreu em pacientes jovens, do sexo masculino, brancos e sulistas. Negros foram afetados desproporcionalmente. A maior parte das lesões oculares relacionadas a armas de fogo apresentou riscos à visão e foi associada a lesões cerebrais traumáticas. A maioria dos pacientes sobreviveu, mas com potencial para invalidez no longo prazo. As diferenças demográficas identificadas podem ser potencialmente alvos de ações preventivas.

Gender of Presenters at Ophthalmology Conferences Between 2015 and 2017.

PURPOSE: To analyze the proportion of women presenting at 9 major ophthalmology conferences over 3 years. DESIGN: Retrospective observational study. METHODS: Conference brochures from 9 national ophthalmology conferences from 2015 to 2017 were analyzed. Genders of first author presenters of papers and non-papers (moderators, presenters at symposia, panel discussions, workshops/instructional courses) were recorded. Comparisons were made to the gender ratio of board-certified ophthalmologists. Student t test and Cochran-Armitage trend test was used for analysis, with significance at P < .05. RESULTS: Of 14,214 speakers, 30.5% were female, statistically higher than the expected 25.4% (P < .001). Paper presenters were 33.1% female (P < .001) and non-paper presenters were 28.5% female (P < .001). When stratified to general or subspecialty conference, general conferences had a higher proportion of women compared to the American Board of Ophthalmology (ABO) expected rates (P < .001) for paper and non-paper presentations. The rates of female presenters increased over the 3 years only at the Association for Research in Vision and Ophthalmology (P = .009). Subgroup analysis showed that women presented 33.1% of papers but only 28.5% of non-paper presentations, which is lower than expected (P < .001). CONCLUSIONS: Our results highlight positive trends: the overall proportions of female speakers exceed ABO estimates of female ophthalmologists. However, the gender gap remains at many subspecialty conferences, especially for non-papers, which are more likely to require invitations rather than being self-submitted. As demographics continue to change, further efforts are needed to assure equitable selection of conference presenters.