Gaggiano C, Gupta V, Agrawal R, De Smet MD, Frediani B, Tosi GM, Paroli MP, Sridharan S, Pavesio CE, Pleyer U, Denisova EV, Babu K, de-la-Torre A, Yang P, Davis JL, Cunningham ET, Carreño E, Goldstein D, Fonollosa A, Cantarini L, Sobrin L, Fabiani C.
Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network. Ophthalmol Ther 2024;13(1):127-147.
AbstractINTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts.
METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey.
RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors.
CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.
Gharahkhani P, He W, Han X, Ong JS, Rentería ME, Wiggs JL, Khawaja AP, Trzaskowski M, Mackey DA, Craig JE, Hewitt AW, Hewitt AW, Macgregor S, Wu Y.
Genome-wide risk prediction of primary open-angle glaucoma across multiple ancestries. medRxiv 2023;
AbstractBACKGROUND: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The disease is often only diagnosed after retinal ganglion cell damage has occurred, with current treatments unable to restore lost vision. Developing risk identification tools for POAG will help enable timely diagnosis and prevent irreparable damage from occurring, especially for ancestry groups (such as African (AFR)) where the disease prevalence is high. Given the heritable nature of POAG, we aim to develop a polygenic score (PGS), which could facilitate earlier POAG risk detection for timely prevention and diagnosis. METHODS: We applied a multi-ancestry multi-trait approach to build powerful PGS for POAG. We first integrated the new and existing genetics data on POAG and two key endophenotypes, intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR). We then leveraged the shared POAG genetic information across European (EUR), AFR and Asian ancestries and between POAG and each of IOP and VCDR to develop PGS for POAG risk prediction. We systematically assessed the PGS prediction power and risk stratification ability in POAG cohorts of different ancestries. RESULTS: Our newly developed PGS showed improved accuracy compared to previous PGS for POAG risk prediction in EUR ancestry. We showed the transferability of PGS based on EUR ancestry in the prediction of POAG status in AFR and Asian ancestries. Utilizing the shared genetic information across ancestries further improved PGS prediction power for POAG in AFR and East Asian (EAS). For individuals with South Asian ancestry, those in the top PGS decile were diagnosed ~18 years earlier than those in the bottom decile. For AFR ancestry, individuals in the top percentile had an odds ratio of 4.08 (95% CI: 2.33-7.45) compared with the remainder of the population using the newly developed AFR-specific PGS. CONCLUSIONS: In the current study, we developed PGS for POAG risk prediction in EUR, Asian and AFR populations. These PGS, to our best knowledge, are the most powerful PGS currently for POAG risk screening and stratification. We believe that our study will lead to improved POAG detection across diverse populations in the future by enabling targeting clinical screening of people at high levels of genetic risk.
, Berry JL, Pike S, Rajagopalan A, Reid MW, Fabian ID, Afshar AR, Alejos A, Alemany-Rubio E, Alfonso Carreras Y, Arazi M, Astbury NJ, Bascaran C, Binkley E, Blum S, Boldt CH, Bonanomi MTBC, Bowman R, Brennan RC, Burton MJ, Calderón-Sotelo P, Jara DCA, Cano MR, Castillo L, Cavieres I, Cerna DQ, Chandramohan A, Chantada GL, Corson TW, Cowan-Lyn KE, Davanzo JM, Demirci H, Coronado RDY, Dimaras H, Macedo CDR, Ericksen C, Fandiño AC, Fernández DDPG, Foster A, Fu LD, Fuentes-Alabi SL, Garcia JL, Pacheco HGN, Girón AV, Goenz MA, Gold AS, Gomel N, Gonzalez E, Gonzalez Perez G, González-Rodríguez L, Graells J, Grigorovski NDAK, Hamel P, Hansen ED, Harbour WJ, Elizabeth Hartnett M, Hassan M, Hubbard BG, Kapelushnik N, Kim JW, Larson SA, Laurenti KD, Leverant AA, Li C, López JP, Luna-Fineman S, Magrath GN, Mallipatna A, Mattosinho CCDS, Mets MB, Miller A, Mruthyunjaya P, Murray TG, Oliver SCN, Oporto J, Ortega-Hernández M, Ossandon D, Morales CPR, Paton KE, Plager DA, Polania RA, Ponce J, Quintero D K, Ramasubramanian A, Ramirez-Ortiz MA, Randhawa JK, Romero L, Salas B, Sánchez GL, Orozco AJS, Sgroi M, Shah AS, Shields CL, Singh AD, Skalet AH, Stacey AW, Stahl ED, Strahlendorf C, Suarez MEC, Superstein R, Leiva FTF, Teixeira LF, Uner OE, Anchaya JKV, Vaughan LO, Villegas VM, Wilson MW, Yaghy A, Yee RI, López AM, Zondervan M.
Retinoblastoma Outcomes in the Americas: a prospective analysis of 491 children with retinoblastoma from 23 American countries. Am J Ophthalmol 2023;
AbstractPURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income=LIC, lower-middle=LMIC, upper-middle=UMIC, high=HIC) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%) and 190 (38.7%) were from LIC, LMIC, UMIC and HIC, respectively. Three-year survival rates in LICs were 60.0% (95% CI, 12.6-88.2) compared to 99.2% (94.6-99.9) in HICs. Death was less likely in patients older than four years (vs. four or younger, HR=0.45 [95% CI, 0.27 - 0.78], P=0.048). Patients with more advanced tumors (e.g., cT3 vs. cT1, HR= 4.65 × 109 [95% CI, 1.25 × 109 - 1.72 × 1010], P<0.001) and females (vs. males, HR=1.98 [1.27-3.10], P=0.04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI, 5.1-25.6) in LMICs and 46.2% (38.8-53.3) in HICs. At three years, 70.1% of cT1 eyes (95% CI, 54.5-81.2) versus 8.9% of cT3 eyes (5.5-13.3) were salvaged. Advanced tumor stage was associated with higher enucleation risk (e.g., cT3 vs. cT1, SHR=4.98 [95% CI, 2.36-10.5), P<0.001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.