bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of neurophysiological findings by portable full‐field electroretinogram in long‐term type 1 diabetics without diabetic retinopathy
Authors: Álvarez Marta Arias , Sopeña‐Pinilla Maria , Fernández‐Espinosa Guisela , Tomas‐Grasa Cristina , Orduna‐Hospital Elvira , Mena Diego Rodríguez , Pinilla Isabel
Published: January 2025

Aims/Purpose: Diabetic retinopathy (DR), a common complication of Diabetes Mellitus (DM), is the primary cause of irreversible blindness among the working‐age population, particularly affecting those with type 1 diabetes (DM1). This condition poses a global health challenge. DR is acknowledged as a neurovascular disease, initially causing neurodegeneration in the cells of the inner retina and glial cells, which leads to both structural and functional changes. The study aimed to identify early functional changes in long‐standing DM1 patients without DR using a portable full‐field electroretinogram (ERG) to enhance management and preserve vision.

Methods: This prospective study included 23 DM1 patients with over 20 years of disease progression without DR, along with a control group of similar ages. Participants underwent clinical history assessment, ophthalmologic examination, and neurophysiologic evaluation using the mydriasis free RETeval portable system, applying the DR evaluation protocol without mydriasis.

Results: The average age of DM1 participants was 48.00 ± 9.77 years, and 51.69 ± 4.75 years for the control group. The average duration of DM1 was 28.69 ± 6.6 years. Among DM1 patients, significant findings included a reduction in the rod response amplitude, an increase in a‐wave implicit time (IT), and a decrease in b‐wave amplitude in the mixed response to 280 Td.s. Additionally, there was an increase in IT and a decrease in the amplitude of OP2 and OP3, as well as an increased IT and decreased amplitude of the response to 16 Td.s at 28.3 Hz. These results were consistent with those obtained using conventional ERG and were statistically significant (p < 0.05).

Conclusions: Long‐standing DM1 patients without DR primarily exhibit ERG alterations under scotopic conditions, especially in oscillatory potentials, when evaluated with the portable ERG system. This emphasizes the importance of using this system for the early detection and monitoring of DR.
Evaluation of cone‐mediated dark adaptation using a smartphone app (MOBILE_DA) in healthy subjects
Authors: Gavilán Beatriz Sánchez , Marin Maria Cinta Puell , Pundlik Shrinivas
Published: January 2025

Purpose: There is evidence of the role of dark adaptation (DA) as a functional biomarker in age‐related macular degeneration (AMD) where foveal cones are impacted during the initial stages of AMD. In this study we determine the repeatability of smartphone application (MOBILE DA) to evaluate the cone‐mediated dark adaptation (DA) in healthy young adults.

Methods: Testing was done by placing a smartphone in front of the subject in a dark room. The App presented a 1.5° flashing stimulus at 3° eccentricity using an adaptive staircase. A 14800 lux white bulb was used for bleaching before testing. In two different sessions 1 week apart, the cone‐mediated dark adaptation was measured in 40 healthy subjects aged 21.4 ± 3.4 with good visual acuity (VA). Cone‐mediated DA recovery threshold was measured for 5 min. Threshold recovery functions were fitted to an exponential decay model to determine the time constant (τ, minutes) of cone sensitivity recovery and final cone luminance threshold (LTf). Repeatability was estimated by the Bland‐Altman method, whereby the mean difference (MD) and the 95% limits agreement were determinate as the coefficient of repeatability (COR).

Results: Mean time constant () values was 1.28 ± 0.43 minutes in session 1 and 1.28 ± 5.4 for the session 2 and for the final luminance threshold the mean values were ‐2.12 ± 0.23 log cd/m2 for the session 1 and ‐2.13 ± 0.28 for the session 2. Mean differences in time constant measurements and LTf between session 1 and 2 were not significant. COR value for was 1minute and COR value for LTf was 0.33 log cd/m2.

Conclusions: The MOBILE‐DA offered repeatable measurements. The APP was able to detect rapid changes in light sensitivity that occur during cone‐mediated dark adaptation indicating the clinical potential of using mobile device based DA measurements.
Carlevale intraocular lens refractive predictability: A retrospective analysis
Authors: Dias Bruno Guerreiro , Matos Diogo Bernardo , Marques‐Neves Carlos , Faria Mun Yueh , Ferreira Nuno Pinto
Published: January 2025

Aims/Purpose: The purpose of this study was to evaluate the refractive predictability of the sutureless scleral fixation Carlevale intraocular lens (IOL) for the correction of aphakia in the absence of capsular support.

Methods: Retrospective cohort study. Consecutive patients implanted with Carlevale IOL between February 2020 and February 2024, with a minimum follow‐up of 3 months, were included. Exclusion criteria included use of toric IOLs and absence of postoperative refraction due to a severely limited visual acuity or lack of cooperation. The clinical data were acquired from the patients' records. Primary outcome was the postoperative spherical equivalent deviation (PSED) in relation to the preoperative refractive target. Secondary outcomes included the best corrected visual acuity (BCVA), surgically induced astigmatism (SIA), and postoperative complications.

Results: A total of 44 eyes were implanted with the Carlevale IOL in the study period. Of these, 30 met the inclusion criteria and were included in the statistical analysis. The mean follow‐up time was 18.3 ± 11.7 months, and the mean age at the time of surgery was 70.93 ± 16.28 years. The most common surgical indications were aphakia after complicated cataract surgery (40%, n = 12), IOL dislocation (33.3%, n = 10), and aphakia after trauma (20%, n = 6). The PSED was ‐0.62 ± 1.51 diopters, with no statistically significant difference between surgical indication groups (p = 0.606). BCVA showed a statistically significant increase from 1.52 ± 0.88 to 0.42 ± 0.41 logMAR (p < 0.001). The trauma group had worse BCVA results (p = 0.013). The SIA was 1.14 ± 1.93 diopters. Regarding postoperative complications, the most common were transient ocular hypertension (20%), bleeding (hyphema or hemovitreous; 13.3%), and cystoid macular edema (6.6%).

Conclusions: The Carlevale IOL is a valuable option in our arsenal for managing aphakic eyes with no capsular support. It appears to provide acceptable predictability in refractive outcomes, with low astigmatism and few associated complications.
Congenital aniridia: experience of 26 years in the department of pediatric ophtalmology of Casablanca, Morocco
Authors: Daghouj Ghizlane , Ettouri Sara , Rokaya Chahir , Rami Ali , El Maaloum Loubna , Allali Bouchra , El Kettani Asmaa
Published: January 2025

Aims/Purpose: Report the experience of 26 years in the department of pediatric ophthalmology in Casablanca.

Methods: Retrospective study from 1996 to 2022 about 30 eyes with congenital aniridia.

Results: The average age is 83.35 months. Male at 53% and female at 47% .46% with nystagmus. 20% of the eyes were with corneal involvement. 56.6% of the lenses are cataract. 30% of lenses were dislocated. 30% of aniridia were associated with glaucoma .33.3% of fundus where passage were possible: 22% were normal and the rest pathological. Glaucoma: 2 of the 9 eyes with glaucoma were operated on and the rest under hypotonic medical treatment. Cataract: 13 operated eyes. All children received optical correction and amblyopia treatment. All abdominal ultrasounds were normal. The gain in visual acuity on average was 1 line after therapeutic measures.

Conclusions: Aniridia is rare but can significantly and progressively impair vision by reaching the entire eyeball with polymorphic manifestations. Management of aniridia remains difficult, it must be both proactive and responsive, with medical or surgical management or both of them. In sporadic forms an abdominal ultrasound is necessary to rule out the presence of Wilms tumor.

References

Efficacy and Safety of Plasma Rich in Growth Factor in Patients with Congenital Aniridia and Dry Eye Disease. Lozano‐Sanroma J, Barros A, Alcalde I, Alvarado‐Villacorta R, Sánchez‐Ávila RM, Queiruga‐Piñeiro J, Cueto LF, Anitua E, Merayo‐Lloves J.Diseases. 2024 Apr 11; 12(4): 76. doi: 10.3390/diseases12040076.

Epidemiology of PAX6 Gene Pathogenic Variants and Expected Prevalence of PAX6‐Associated Congenital Aniridia across the Russian Federation: A Nationwide Study. Vasilyeva TA, Marakhonov AV, Voskresenskaya AA, Kadyshev VV, Sukhanova NV, Minzhenkova ME, Shilova NV, Latyshova AA, Ginter EK, Kutsev SI, Zinchenko RA.Genes (Basel). 2023 Nov 4; 14(11): 2041. doi: 10.3390/genes14112041.

Congenital aniridia and cataract. C. Speeg‐Schatz. Journal francais d’ophtalmologie, Volume35‐ N°4, Avril 2012. Doi: 10.1016/j.jfo.2011.04.017
Whole genome sequencing requested directly from a multi‐ethnic london adult retinal clinic
Authors: Jabarkhyl Dost , Jeste Mrunmayi , Chow Isabelle , Mohamed Moin , Mahroo Omar
Published: January 2025

Aims/Purpose: Physicians in the UK can now request whole genome sequencing (WGS) for suspected inherited retinal disease (IRD), funded by a National Genomic Medicine Service. Achieving genetic diagnoses can be more challenging for ethnicities with lower representation in reference genomes. We report initial results from a specialist adult retinal service, with no prior experience of direct genetic testing from clinic.

Methods: WGS was undertaken with screening of a virtual panel of known IRD‐associated genes. Exceptions to WGS included suspected albinism and pseudoxanthoma elasticum, where targeted sequencing was undertaken of albinism‐associated genes or ABCC6 respectively.

Results: To date, results for 28 patients (mean (SD) age, 51 (17) years; 17 females) from 27 families have been received. Ethnicities were white European (13), African (9), South Asian (3), and mixed (3). Reports were positive in 15 cases (variants in ABCA4, BEST1, USH2A, TYR, COL18A1, RHO, ABCC6, PRPF8, CRB1, EFEMP1, NR2E3, CNGB3, CERKL) and were consistent with the clinical phenotype. Ten reports were negative and 3 were inconclusive. In 2 of the latter, the phenotype was sufficiently specific (Bietti crystalline dystrophy and Oguchi disease) to allow attribution of disease to variants found in CYP4V2 and GRK1 respectively. Of 17 patients achieving a genetic diagnosis, 9 were white European, 6 were of African origin, 1 South Asian, and 1 of mixed ethnicity). Mean (SD) time between patient consent and report availability was 9.0 (2.5) months.

Conclusions: In this analysis of tests performed so far from a clinic serving a multi‐ethnic patient population, a molecular diagnosis was achieved in 61% of patients. The phenotype continues to be important for correctly interpreting genetic data. Achieving genetic diagnosis allows confirmation of genetic aetiology, more informed counselling relating to risk to children, and determines eligibility for the increasing number of gene‐directed experimental therapies.
Genome‐wide association study of anterior uveitis
Authors: Koskimäki Fredrika , Ahokas Oona ,   FinnGen Consortium,   Estonian Biobank Research Team, Elnahas Abdelrahman , Reigo Anu , Reis Kadri , Esko Tõnu , Palta Priit , Leinonen Sanna , Kettunen Johannes , Liinamaa Johanna , Karjalainen Minna , Saarela Ville
Published: January 2025

Aims/Purpose: The purpose of this study was to identify new genetic associations of anterior uveitis through genome‐wide association study (GWAS).

Methods: We conducted a GWAS meta‐analysis combining data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 cases and 917 145 controls. A phenome‐wide association study was performed to investigate associations across phenotypes and traits. Genetic correlations of anterior uveitis were evaluated.

Results: We detected six anterior uveitis associated genomic regions with genome‐wide significance (p < 5 × 10‐8). Three novel loci were identified: INAVA, NLRP3 and NOS2. Three previously reported associations at HLA region, ERAP1 and TNRC18 were detected. All of these loci had biologically relevant genes involved in immunity. We also replicated associations at two loci previously associated with acute anterior uveitis (IL23R and HDAC2‐AS2). Phenome‐wide association study indicated that lead SNPs at three of the anterior uveitis associated loci (ERAP1, INAVA and TNRC18) are associated with other immunity‐related phenotypes, including ankylosing spondylitis and inflammatory bowel disease. A moderate genetic correlation between anterior uveitis and inflammatory bowel disease was found in genetic correlation analysis (rg = 0.39, p = 8 × 10‐5).

Conclusions: We identified six anterior uveitis associated loci including three novel loci with genome‐wide significance. Our findings deepen our understanding of the genetic basis of anterior uveitis and the genetic connections between anterior uveitis and immune related disorders, providing a foundation for further research and potential therapeutic interventions.
GPT wars: Creating and detecting fake ophthalmology data sets with artificial intelligence
Authors: Taloni Andrea , Coco Giulia , Pellegrini Marco , Lucisano Andrea , Scalzo Giovanna Carnovale , Scorcia Vincenzo , Giannaccare Giuseppe
Published: January 2025

Aims/Purpose: Recently, our group demonstrated how the Large Language Model GPT‐4 can fabricate fake ophthalmology data sets, designed to support false scientific evidence. The objectives of this study were: (1) to identify peculiar statistical patterns of AI‐generated data sets, (2) to attempt at enhancing the quality of fabricated data for eliminating any discernible mark of non‐authenticity, and (3) to develop a custom GPT trained to detect signs of fabrication.

Methods: Three fictional studies were designed to compare treatment outcomes for a specific ocular disease. First, prompts were submitted to the custom GPT “Data Analyst” to produce 12 “unrefined” fake data sets for the three studies. Then, the custom GPT “Fake Data Creator” was developed to generate 12 “refined” fake data sets, specifically designed to evade authenticity checks. Forensic analysis was performed on all data sets using IBM SPSS. Finally, the custom GPT “Fake Data Detector” (FDD) was developed to replicate the forensic analysis and assign 1 point for each sign of fabrication.

Results: Forensic analysis of the unrefined fake data sets revealed numerous flaws, most notably: name/gender mismatch (n = 12), non‐uniform distribution (n = 11) and repetitive patterns of last digits (n = 7), absence of correlation between study variables (n = 12), and distribution shape anomalies (n = 11). In refined fake data sets, the forensic analysis did not reveal statistical flaws, except for distribution shape anomalies (n = 7). Overall, 5 refined fake data sets (41.7%) passed forensic analysis as authentic. The results of the statistical analyses performed by GPT FDD were identical to those obtained with IBM SPSS, with a mean of 9.67 ± 2.13 (95% IC 8.46‐10.87) and 1.00 ± 1.00 (95% IC 0.43‐1.57) points respectively allocated to unrefined and refined data sets.

Conclusions: Sufficiently sophisticated custom GPTs can perform complex statistical tasks and may be abused to fabricate seemingly authentic ophthalmology data sets, passing forensic analysis.

References

Taloni A, Scorcia V, Giannaccare G. Large Language Model Advanced Data Analysis Abuse to Create a Fake Data Set in Medical Research. JAMA Ophthalmol. 2023; 141(12): 1174–1175. doi: 10.1001/jamaophthalmol.2023.5162
Retinal ischemia: Therapeutic effects and mechanisms of paeoniflorin
Authors: Chao Winsdor Wen‐Jin , Chao Howard Wen‐Haur , Chao Hsiao‐Ming
Published: January 2025

Aims/Purpose: Retinal ischemia‐associated ocular disorders are vision threatening. The aim of the present study is to assess the potential of paeoniflorin in alleviating retinal ischemic injury and to uncover the mechanisms involved.

Methods: Cultured retinal cells were subjected to oxygen glucose deprivation (OGD; N2/CO2/O2: 95 %/5 %/1 %) with pre‐OGD (1h) administration of paeoniflorin (0.25/0.5 mM). The cell viability were evaluated by MTT assay.

High intraocular pressure‐induced retinal ischemia (I) was established by raising IOP to 120 mmHg for 60 minutes followed by reperfusion (R) for 7 days in an ischemic eye in a Wistar rat. The physiological effects of the retina were evaluated by electrophysiology and fluorogold retrograde labelling RGCs. The protein levels of angiopoietin, pyruvate kinase M2 (PKM2), Wnt3a and β‐catenin were assessed by Western blotting.

Results: Pre‐ischemic administration of paeoniflorin dose‐dependently (less effect at 0.25 mM) and significantly (p < 0.05; 0.5 mM) alleviated OGD induced significant (p < 0.001) decrease in RGC‐5 cell viability. Furthermore, pre‐ischemic administration of paeoniflorin dose‐dependently (less effect at 0.25 mM) and significantly (p < 0.05/p < 0.001; 0.5 mM) attenuated ischemia‐induced significant (p < 0.001/p < 0.05) reduction in ERG b‐wave amplitude/RGC cell number.

Compared to eyes treated with vehicle, paeoniflorin (p < 0.05/p < 0.01/p < 0.05; 0.5 mM) seemed to protect against retinal ischemia by regulating angiopoietin, β‐catenin, WNT and PKM2 expression.

Conclusions: The treatment with paeoniflorin is able to effectively reduce retinal ischemia by affecting angiopoietin, β‐catenin, WNT and PKM2 biomarkers.

References

Windsor Wen‐Jin Chao, Howard Wen‐Haur Chao, Hung‐Fu Lee, Hsiao‐Ming Chao. The Effect of S‐Allyl L‐Cysteine on Retinal Ischemia: The Contributions of MCP‐1 and PKM2 in the Underlying Medicinal Properties. Int J Mol Sci. 2024 Jan 22; 25(2): 1349.

Chao HM, Osborne NN. Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)‐adrenoceptors and not by an action on imidazoline receptors. Brain Res. 2001 Jun 15; 904(1): 126‐36.
Iris, ciliary body and choroid metastasis from salivary duct carcinoma of parotid gland: Case report
Authors: Lobo Vasco , Monteiro Bernardo , Whitfield Rafael , Alvim Cecília , Pinto Filomena
Published: January 2025

Aims/Purpose: Report a rare case of salivary duct carcinoma (SDC) of the left parotid gland metastatic to the iris, ciliary body and choroid.

Methods: Data collection from clinical records.

Results: A 70‐year‐old woman with a history of stage IV SDC of the left parotid (pT2 cNx cM1) diagnosed in November 2020, treated with palliative chemotherapy with cisplatin since October 2021, presented to Ophthalmology department in Hospital de Santa Maria, Lisbon, Portugal in November 2021 due to a solid lesion in the anterior chamber and progressive declining vision of the left eye. Ultrasound biomicroscopy showed a 6.7x12.0x4.7mm cupuliform mass in the iris, with high reflectivity and heterogeneous internal structure, involving the ciliary body and displacing posteriorly the intraocular lens. Posterior segment ultrasound revealed a solid cupuliform lesion of the ocular wall, approximately 3 mm thick, with high reflectivity and a heterogeneous structure. The ultrasound characteristics were consistent with secondary intraocular lesion of the iris, ciliary body and choroid and orbital MRI supported this diagnosis. In December 2021, due to global systemic progression after three cycles of cisplatin, the patient was switched to 9 cycles of doxorubicin+cyclophosphamide, with apparent stabilization of the systemic disease. In September 2022, there was a significant reduction in the size of the iris metastasis, even though the posterior segment ultrasound demonstrated progression of the intraocular disease, now with multifocal choroidal metastasis in both eyes, associated with exudative detachment of the retina in the right eye. Due to multiple cerebral metastasis, the patient underwent holocranial radiotherapy 30 Gy/10 fractions, with ophthalmological findings being unchanged in October 2022. She underwent two more cycles of paclitaxel, which was suspended due to clinical deterioration. The patient died in December 2022, with a survival of 25 months (13 months since diagnosis of intraocular metastases).

Conclusions: The case reports a rare presentation of metastatic SDC to the eye.
Sentinel lymph node biopsy in a case of conjunctival melanoma
Authors: Rius Nuria , Ciobotaru Olga , Sopeña‐Pinilla Maria , Merino Jacobo Yañez , Funes Elisa , Munuera Inés , Santana Carlos , Navarro Damián García , Monleón Claudia Hernández‐Barahona , Ila Carmen
Published: January 2025

Aims/Purpose: To present the first case of a sentinel lymph node biopsy for ocular melanoma in our hospital.

Methods: We present the clinical case of a patient treated in our unit for conjunctival melanoma in the right eye. An excision of the conjunctival lesion with safety margins was performed, followed by the application of mitomycin C, cryotherapy, and placement of an amniotic membrane. The histopathological diagnosis confirmed an invasive nodular melanoma pT2aNxMx Breslow 1.5 mm with clear margins. Subsequently, three weekly cycles of 0.04% mitomycin C eye drops were administered. The extension study ruled out disease dissemination.

Results: The case was presented to the Melanoma Committee, where it was decided to perform a sentinel lymph node biopsy. The procedure was carried out without evidence of metastasis in the analyzed lymph node (0/1), confirmed by histological examination with Hematoxylin‐eosin and immunohistochemistry with HMB45 and SOX10. This is the first case of a sentinel lymph node biopsy for ocular melanoma in our hospital. Thanks to close collaboration between the Ophthalmology and Radiology departments, the procedure was performed correctly.

Currently, the patient continues with successive follow‐ups by Ophthalmology, showing good evolution. This case highlights the importance of interdisciplinary collaboration in the management of conjunctival melanoma and the efficacy of adjuvant treatments, such as mitomycin C, in preventing local recurrences

Conclusions: Current literature supports the performance of sentinel lymph node biopsy in cases of conjunctival melanoma due to its ability to detect micrometastases and guide therapeutic management, thus improving patient prognosis. It is a valuable tool in the accurate staging of conjunctival melanoma, allowing for earlier intervention in case of lymphatic dissemination and potentially improving survival rates.
Dexmedetomidine as a therapeutic approach for retinal degeneration
Authors: Kalatanova Anna , Leinonen Henri
Published: January 2025

Aims/Purpose: Gene therapy shows great promise in multiple types inherited retinal degenerations (IRDs); however, the genetic diversity of these diseases also requires mutation‐agnostic therapeutic approaches to be developed. This study investigates the potential of dexmedetomidine, an alpha‐2 agonist, as a neuroprotectant for IRDs.

Methods: We investigated the efficacy of dexmedetomidine in two different in vivo paradigms: acute light‐induced retinal degeneration (LIRD), and the rd10 mouse model of RP. The rd10 mouse is a highly translationally relevant RP model and it carries a spontaneous mutation in the Pde6b gene, like that found in human patients. LIRD was induced to BALB/c mice that received dexmedetomidine (0.01‐0.03 mg/kg) or vehicle intraperitoneally 30‐min before light exposure (15 kLux for 30 mins). In rd10 mice, dietary dexmedetomidine (1 mg/100g in standard chow) administration between postnatal ages 30 and 51 days was used. Optical coherence tomography (OCT) and electroretinography (ERG) were used to evaluate drug efficacy in both paradigms.

Results: In the LIRD model, dexmedetomidine 0.03 mg/kg led to near‐complete retina protection. With this dose, ERG a‐waves were comparable to baseline levels. Instead, in vehicle‐treated mice, 93% decrease in a‐wave amplitude compared to baseline was found. OCT imaging revealed an 81% decrease in the outer nuclear layer in the vehicle group, whereas it was nearly normal in mice treated with 0.03 mg/kg dexmedetomidine. In rd10 mice, dietary dexmedetomidine improved ERG responses; by approximately 53% at the highest intensity stimulus when measured at P51.

Conclusions: These promising results with systemic drug delivery prompts further research into developing an ocular administration method for dexmedetomidine. Locally administered neuroprotectants could lead to therapeutic approaches in IRDs.
Longitudinal changes in the inner retina in long‐term evolution type 1 diabetic patients without diabetic retinopathy evaluated by optical coherence tomography
Authors: Fernández‐Espinosa Guisela , Martínez‐López Alba , Orduna‐Hospital Elvira , Sopeña‐Pinilla María , Boned‐Murillo Ana , Arias‐Álvarez Marta , Díaz‐Barreda María Dolores , Sánchez‐Cano Ana , Pinilla Isabel
Published: January 2025

Aims/Purpose: To assess longitudinal changes in the thickness of the inner retinal layers in long‐term evolution type 1 diabetes mellitus (DM1) patients without signs of diabetic retinopathy (DR), evaluated using optical coherence tomography (OCT) at three time points over 14 years.

Methods: A prospective longitudinal study was conducted, including 33 eyes of 33 DM1 patients with over 24 years of disease evolution and good glycaemic control (HbA1c). Patients had been previously evaluated in 2009 and 2017. The total sample in 2023 that did not develop DR consisted of 33 eyes. A complete ophthalmological examination was performed, including assessment of total retinal thickness and inner retinal layers (ganglion cell layer (GCL), and retinal nerve fiber layer (RNFL)), using Spectralis spectral‐domain OCT (SD‐OCT).

Results: After evaluating the image quality, 3 eyes were excluded. The final sample consisted of 30 DM1 eyes, with a mean age of 41.47 ± 9.63 years and a disease evolution of 28.60 ± 7.87 years. There was a statistically significant decline in visual acuity (VA). A decrease in total retinal thickness in all areas except the temporal external (TE); the GCL showed a decrease in all areas except the TE and the nasal external (NE): RNFL exhibited an increased thickness of the temporal internal (TI), superior external (SE), and inferior external (IE) with reduced thickness in the inferior internal (II) area. There was a negative correlation between HbA1c levels and the average thickness of both the RNFL and GCL.

Conclusions: After 14 years of follow‐up, DM1 patients without DR showed a decrease in the total retina thickness and the GCL layer thickness, with less conclusive changes in the RNFL thickness. VA diminished during the disease despite maintaining good glycaemic control. Glycaemic control was related to a decrease in the thickness of the studied layers.
Clinical patter of uveitis masquerade syndrome: A fifteen‐year retrospective case series
Authors: Kammoun Nour , Abroug Nesrine , Wijdene Nabi , Eahma Bel Hadj , Bechir Jelliti , Khairallah Moncef
Published: January 2025

Aims/Purpose: To describe the clinical pattern of uveitis masquerade syndrome (UMS).

Methods: A retrospective descriptive monocentric study between January 01, 2007 and December 31, 2022.

Results: Over a 15‐year period, we identified 89 cases (124 eyes) among 3,000 cases of uveitis, with a final diagnosis of UMS, i.e. a rate of 3%. Thirty cases (33.7%) were neoplastic UMS and 59 cases (66.3%) were nonneoplastic UMS. The mean age was 40 ± 19 years (extremes; 7 – 80 years), including 43 men (48.3%) and 46 women (51.7%). Ocular involvement was unilateral in 61% of cases. Time to diagnosis ranged from 1 day to 10 years, with an average of 4.7 months. Etiologies of neoplastic UMS were malignant tumors (19 cases; 63%), including vitreoretinal lymphoma (7 cases; 37%), uveal melanoma (6 cases; 31%), ocular metastases (5 cases; 26%) and one case of leukemia, benign tumours (8 cases; 26.6%) and paraneoplastic syndromes (3 cases; 10%). Hereditary retinal dystrophies were the main etiology of non neoplastic UMS (17 cases; 28.8%), followed by rhegmatogenous retinal detachment (7 cases; 11.8%). Prior to the final diagnosis, a therapeutic mistake was found in 19% of cases including prescribing topical and/or systemic corticosteroids and immunosppressive therapy.

Conclusions: In our series, vitreoretinal lymphoma and hereditary retinal dystrophies were the main etiologies of UMS. Meticulous analysis of the patient's history and ocular clinical and imaging findings is mandatory to avoid diagnostic and therapeutic mistakes
Up to 10‐month outcomes of faricimab in treating treatment‐refractory wet age‐related macular degeneration
Authors: Tay Nicole , Milczynska Wiktoria , Kogiantis Alexandros
Published: January 2025

Aims/Purpose: Wet Age‐Related Macular Degeneration (ARMD) represents a significant irreversible cause of blindness worldwide. Current treatment options are limited to anti‐VEGF therapy, which has shown limited success in halting disease progression. A novel anti‐VEGF therapy, Faricimab, has been suggested to revolutionise these outcomes. This study aimed to evaluate the effectiveness of Faricimab in treating Wet ARMD.

Methods: This retrospective cohort study was conducted. Inclusion criteria: all patients with a diagnosis of Wet ARMD who received at least 4 loading‐doses of Faricimab between January 2023 and May 2024 at Watford General Hospital, United Kingdom. Exclusion criteria: Patients who did not receive any anti‐VEGF treatments prior to starting Faricimab. Data on visual acuity (VA) and OCT images were collected for their first and last injections. OCTs were analysed to evaluate the thickness of central retinal fluid (CRF), pigment epithelial detachment (PED) and sub‐retinal fluid (SRF). Data was compared between increasing number of Faricimab injections, OCT thicknesses and visual outcomes.

Results: 40 patients (45 eyes) were identified and included in the study. The mean change of thickness between first and last injections in patients were: +1.18 ± 35.7 % increase in CRF, ‐1.65 ± 39.7 % decrease in PED, and ‐40.053 ± 52.4 % of the patients who had SRF. There was no significant difference in CRF or PED thickness changes between 4‐6 injections compared to 8‐10 injections (p: 0.39 and p: 0.17). Average VA worsened, with a mean of 0.065 ± 0.475 increase in LogMAR.

Conclusions: This study demonstrates the limited effectiveness of Faricimab in treating wet ARMD. There was no significant decrease in CRF and PED. However, there was a 40% decrease in SRF for patients affected by pre‐existing SRF before the 4th injection. Current literature indicates a link between a reduction in SRF and a subsequent worsening in VA1, as seen in our study. Further data needs to be collected to assess the effectiveness of Faricimab in treating ARMD.

References: 1 Siedlecki J et al. Impact of Sub‐Retinal Fluid on the Long‐Term Incidence of Macular Atrophy in Neovascular Age‐related Macular Degeneration under Treat & Extend Anti‐Vascular Endothelial Growth Factor Inhibitors. Sci Rep. 2020 May 15; 10(1): 8036. doi: 10.1038/s41598‐020‐64901‐9.
Regarding a case, can hypertrophy of the retinal pigment epithelium be the first sign of familial adenomatous polyposis?
Authors: Rafecas Ariadna Garreta
Published: January 2025

Aims/Purpose: Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) is a benign ocular condition characterized by well‐demarcated, flat, pigmented lesions in the retinal pigment epithelium. The primary aim of studying CHRPE is to understand its prevalence, features, and potential associations with other conditions, particularly familial adenomatous polyposis coli (FAP), which can have significant health implications.

Methods: With an example clinical case, methods for studying CHRPE often involve comprehensive eye examinations using tools like the Optomap imaging system, which provides ultra‐wide‐field views of the retina, enabling detailed observation of the lesions.

Results: Results from studies have shown that CHRPE has a low prevalence rate and is typically found temporally to the optic disc within the peripheral fundus. The lesions are usually monocular and exhibit a range of documented shapes and sizes. Some lesions present with depigmented haloes and lacunae, which are atrophied window‐like defects. The progression of CHRPE is not well‐documented due to the lack of longitudinal follow‐up in most studies. However, there is evidence suggesting that the lesions may increase in size due to atrophy over time. Conclusions drawn from the research indicate that CHRPE is generally not associated with symptoms or visual impairment, and its presence does not necessarily indicate a link with syndromes like FAP, Gardner's, or Turcot's.

Conclusions: This conclusion is significant as it helps differentiate CHRPE from similar retinal conditions that may have more serious implications. For further reading on the prevalence and ocular features of CHRPE in the optometric population, one can refer to the study by Coleman and Barnard. Additionally, the imaging characteristics of CHRPE have been described in detail in a retrospective observational case series, which provides insights into the lesion's features as analyzed by enhanced‐depth imaging optical coherence tomography.

References: Deibert B, Ferris L, Sanchez N, Weishaar P. The link between colon cancer and congenital hypertrophy of the retinal pigment epithelium (CHRPE). Am J Ophthalmol Case Rep. 2019 Sep; 15: 100524.
Treatment of polypoidal choroidal vasculopathy in the real world and its underlying mechanisms
Authors: Chao Howard Wen‐Haur , Chao Hsiao‐Ming
Published: January 2025

Aims/Purpose: To evaluate the efficacy of combined therapy (verteporfin PDT plus anti‐VEGF) vs. anti‐VEGF monotherapy in symptomatic macular polypoidal choroidal vasculopathy (PCV) and its underlying therapeutic mechanisms.

Methods: In this retrospective indocyanine green angiography (ICG)–proved PCV study, 21 Chinese (mean age: 67.50 ± 2.22 years; 17 males; 4 females; 11 left eyes) were treated randomized to mainly verteporfin PDT (standard fluence) + anti‐VEGF, or anti‐VEGF monotherapy. Patients were followed monthly by 3D OCT and re‐treated if signs/symptoms (e.g. cystoid macular edema/deteriorated best corrected vision, BCVA) recurred or persisted. Patients were evaluated with ICG to observe the regression of polyps. Change in BCVA/central retinal thickness, CRT, and safety were also included.

Results: The mean follow‐up period (37.04 ± 7.74 months) showed that verteporfin PDT combined with antibodies (bevacizumab, ranibizumab or aflibercept) was compared to anti‐VEGF monotherapy in reducing the CRT (151.75 ± 40.37μm vs. 151.00 ± 58.83); BCVA changes (LogMAR) were ‐0.01 ± 0.21 (verteporfin PDT+antibodies) vs. 0.08 ± 0.09 (anti‐VEGF monotherapy). The mean injection numbers are 1.1# PDT+2# anti‐VEGF agents for combined therapy; 4.6 ± 1.2 anti‐VEGF agents for monotherapy. Three patients of PCV (30%) were recurrent and averaged 18.50 ± 9.26 months. Incomplete remission of polyps/BVN were observed in all eyes. There were no new safety issues with defined therapies. The PCV/nvAMD (control) levels of PLGF, VEGF, HIF1α and Wnt were 3.60 ± 1.48 (n = 8)/32.45 ± 10.53 (n = 28), 105.52 ± 16.15 (n = 8)/235.38 ± 42.13 (n = 27), 2.78 ± 1.40 (n = 3)/2.27 ± 0.43 (n = 63) and 2.13 ± 1.22 (n = 5)/2.40 ± 0.34 (n = 20). As compared to nvAMD, those concentrations of PLGF and VEGF in PCV were much lower.

Conclusions: Verteporfin PDT plus antibodies was compared to anti‐VEGF monotherapy in achieving less number of visits/injections in this study in symptomatic macular PCV. However, BCVA was only stable (‐0.01 ± 0.21) but not improved, which was not correlating to the anatomic improvement. All treatments were well tolerated over the around 2‐year follow‐up period. As shown by various biomarkers, PCV should be a variant of nvAMD. It might therefore explain dissimilarity in response to anti‐VEGF and/or PDT treatment.
Vascular density and metamorphopsia after successful repair of rhegmatogenous retinal detachment. comparison between macula‐on and macula‐off eyes
Authors: Xirou Tina , Smoustopoulos Georgios , Kontou Evgenia , Garnavou‐Xirou Christina , Gkizis Ilias , Bontzos George
Published: January 2025

Purpose: To analyze vascular changes such as the postoperative foveal avascular zone (FAZ) area, the superficial vessel density (sVD) and deep vessel density (dVD) and their correlation with functional (best‐corrected visual acuity, metamorphopsia) and anatomical variables (foveal macular thickness, FMT) after successful repair of a rhegmatogenous retinal detachment (RRD) repair.

Methods: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas or silicone oil tamponade and a minimum 6 months follow‐up, were re‐examined. For patients where silicone oil was applied, measures were taken after its removal. Foveal avascular zone (FAZ) area, sVD, dVD and FAZ area were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye. Moreover, anatomical association was tested between areas of reported metamorphopsias and vascular changes in the corresponding area.

Results: Twenty‐one patients with macula‐on and 24 with macula‐off RRD were included in the study. In both groups, no significant difference in macular thickness and FAZ area was found compared to fellow eyes. In macula‐on RRD eyes, a lower total dVD (p < 0.05) was detected; FAZ area was not related to FMT, and the postoperative BCVA was correlated with FAZ area and dDV (p < 0.05). In macula‐off RRD eyes, lower sDV (p = 0.05), and dVD (p < 0.05, respectively) were observed when compared to fellow eyes. The prevalence of metamorphopsia in macula‐on group was 42.86% (9/21), whereas in macula ‐off this number increased to 62.5% (15/24). For both of these groups we found significant association between sDV and presence of metamorphopsia but only in the inferior paramacular area (p = 0.01).

Conclusions: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower vessel density in the superficial and deep retinal plexus compared to fellow healthy eyes; final BCVA was related to vessel density and FAZ area. Metamorphopsias were also related to superficial vessel density inferiorly of the macula.
Advanced glycation end products association with diabetic retinopathy severity
Authors: Varoniukaite Aiste , Verkauskiene Rasa , Simoniene Diana , Paskeviciene Deimante , Balciuniene Vilma
Published: January 2025

Aims/Purpose: Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result to exposure to sugars and diabetes (DM) can accelerate its usually slow accumulation. Higher levels of AGEs are associated with microvascular complications as diabetic retinopathy (DR). AGEs can be measured in human skin using ultra‐violet light to excite autofluorescence. The purpose of this study was to determine the association between AGEs levels and DR severity.

Methods: A total of 152 patients were enrolled. DR severity was determined by an ophthalmologist. AGEs concentrations were measured with non‐invasive AGE Reader device.

Results: 69 men and 83 women with type 1 (50.7%) and type 2 (49.3%) diabetes were included in the analysis. Age median was 51.85 (min.18, max. 85) years with duration of diabetes 15.99 ± 11.18 years. Mean HbA1C was 8.34 ± 1.99%. 43.7% had no signs of DR, 40.4% had non‐proliferative DR (NPDR), 15.9% – proliferative DR (PDR). Age and HbA1C did not differ between different severity DR groups (p = 0.081 and p = 0.196). AGEs concentration increases with age (r = 0.498, p < 0.001) and duration of diabetes (r = 0.308, p < 0.001). Mean concentration of AGEs were higher in type 2 DM group (p = 0.015). The concentration of AGEs did not differ between DR groups (p = 0.473), thought in type 1 DM subgroup mean concentration of AGEs was higher in PDR patients compared to no DR patients (1.89 vs. 2.43, p = 0.006), whereas no significant difference was found between type 2 DM patients in different DR groups (p = 0.343). There was no significant correlation between HbA1C and AGEs concentration (p = 0246) in all DM patients, but in type 1 DM, AGEs concentration significantly increases with higher HbA1C values (r = 0.309, p = 0.007), but not significantly in type 2 DM (p = 0.282).

Conclusions: The levels of AGEs might have association with the severity of DR in type 1 diabetes, but not type 2. More investigations regarding the association of AGEs and DR severity should be performed.
Neovascular age‐related macular degeneration on three nationwide survey and register data in Finland during 2000–2017
Authors: Purola Petri , Koskinen Seppo , Kaarniranta Kai , Uusitalo Hannu
Published: January 2025

Purpose

To evaluate time trends in the incidence and prevalence of neovascular age‐related macular degeneration (nAMD) and its treatments, associated factors, and effects on vision in Finland during 2000–2017.

Methods

We used three nationwide health examination surveys representing the Finnish population aged 30 years or older. All three surveys were linked to the national care register covering nAMD diagnoses and intravitreal injections between 2000 and 2017. All three surveys included a health examination in which distance and near visual acuity (VA) were measured, as well as self‐reported and register‐based information on socio‐demographic status and lifestyle, health care use, co‐morbidities, and quality of life. The data included two cross‐sectional time points in 2011 and 2017 and two 11 year longitudinal follow‐ups during 2000–2011 and 2006–2017.

Results

The incidence and prevalence of nAMD were two times higher in women than in men. The annual prevalence of nAMD increased from 0.51% to 0.70% and from 0.22% to 0.46% in treated nAMD between 2011 and 2017. Treated nAMD patients had an average of 4 intravitreal injections per treatment year. nAMD patients showed significantly poorer distance and near VA than persons without any AMD in 2011 and 2017 (p < 0.001). However, near VA was significantly better in 2017 than in 2011 among nAMD patients (p = 0.036). The duration of nAMD showed weak negative correlation with distance and near VA. After adjusting for age and sex, nAMD patients showed significantly higher univariable odds ratios for lower distance VA, low consumption of vegetables, living in central Finland, a higher number of hospitalisations per year, and older age compared with persons without any AMD.

Conclusion

Since nAMD is an increasing burden for public health with gender discrepancy and a detrimental impact on vision, we should better find patients who have a high risk of developing nAMD and try to optimise their preventive intervention. Once nAMD is developed, we should understand treatment and follow‐up demands at the personalised level. The nationwide register data help us in those challenges.
A Phase I, First‐In‐Human Study of CBA‐1205, an Anti‐DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors
Authors: Katsuya Yuki , Ikeda Masafumi , Koyama Takafumi , Sato Jun , Okada Mao , Matsubara Nobuaki , Kondoh Chihiro , Mukohara Toru , Watanabe Kazuo , Kotani Daisuke , Ogawa Yoshimi , Taoka Shose , Yamamoto Noboru
Published: January 2025

CBA‐1205 is a novel humanized antibody targeting delta‐like 1 homolog (DLK1) that enhances antibody‐dependent cellular cytotoxicity activity. DLK1 overexpression has been reported in various cancer types, such as hepatocellular carcinoma and neuroblastoma. CBA‐1205 demonstrates potent antitumor activity in multiple tumor models, making it a potential treatment option for DLK1‐expressing cancers. This first‐in‐human, open‐label Phase I study includes three parts. Part 1, the dose‐escalation phase, primarily evaluates the safety profile, tolerability, and maximum tolerated dose of CBA‐1205. The drug is administered intravenously every 2 weeks in a 28‐day cycle. A standard 3 + 3 dose‐escalation design was used across seven cohorts. In a cohort of 22 Japanese patients, over 80% had undergone three or more prior treatments. CBA‐1205 was well tolerated, with no dose‐limiting toxicity observed at doses ranging from 0.1 to 30 mg/kg, the planned highest dose. There were no treatment‐related serious adverse events or trial‐related deaths. CBA‐1205 exposure, as measured by Cmax, AUC0–14, and AUC0–∞, increased in a dose‐dependent manner. No serum anti‐CBA‐1205 antibodies were detected. Serum DLK1 concentrations were found in 6 out of 22 patients. Stable disease for over 6 months was observed in six patients, with progression‐free survival ranging from 29 to 144 weeks. CBA‐1205 was well tolerated, showing no severe toxicity in patients with advanced or recurrent solid tumors. The favorable safety profile and indications of potential activity support further investigation in Parts 2 and 3 of this Phase I study to evaluate the safety, tolerability, and preliminary efficacy of CBA‐1205.
Promoting Identity Development, Multicultural Attitudes, and Civic Engagement Through Ethnic Studies: Evidence From a Natural Experiment
Authors: Gillespie Sarah , Morency Mirinda M. , Fajemirokun Elizabeth , Ferguson Gail M.
Published: January 2025

This study used a natural experiment design to examine the impact of ethnic studies courses on students' ethnic‐racial identity (ERI) development, multicultural attitudes, and civic engagement during the 2021–2022 school year in Minneapolis, MN (N = 535; 33.5% White, 29.5% Black, 21.1% Latine, 10.7% multi‐racial; 44.7% female, 7.1% non‐binary). Compared to students who were quasi‐randomly assigned to a control class, 9th graders taking an ethnic studies class (treatment group) engaged in significantly more midpoint ERI exploration (β = 0.12), resulting in stronger endpoint ERI resolution (β = 0.48–0.57). Increased exploration mediated more favorable attitudes toward multiculturalism (indirect effect = 0.05) and more frequent civic engagement activities (indirect effect = 0.02). Results have implications for policy efforts to expand ethnic studies.
Trajectories of Maternal Urinary Iodine Concentration Are Associated With Gestational Diabetes Mellitus
Authors: Li Yahui , Gu Simeng , Mo Zhe , Li Xueqing , Jiang Yujie , Liu Chenyang , Guo Fanjia , Mao Guangming , Wang Yuanyang , Huang Xuemin , Li Hong , Chen Zhijian , Wang Xiaofeng , Lou Xiaoming
Published: January 2025

Objectives

The relationship between iodine status and gestational diabetes mellitus (GDM) is inconclusive. This study aimed to explore the trajectories of urinary iodine concentrations (UIC) in pregnant women before GDM diagnosis and to assess the associations between maternal UIC trajectories and the risk of developing GDM.

Methods

A prospective cohort study was conducted in China. Data from 1076 pregnant women who were recruited between August 2019 and December 2021 were analyzed. GDM screening was performed at the 28th week of pregnancy. Arsenic and cerium catalysis spectrophotometry was used to measure UIC. The latent class model was used to identify distinct UIC trajectories in pregnant women, using multiple urine specimens. We evaluated the association of UIC trajectories with the risk of GDM by logistic regression analysis.

Results

Three maternal UIC trajectories were identified: (1) high‐stable trajectory (72.12%), (2) high‐decreasing trajectory (3.07%), and (3) low‐stable trajectory (24.81%). Compared with the pregnant women in high‐stable trajectory group, women in the low‐stable UIC trajectory group showed an increased risk of GDM before adjustment of covariates (OR: 1.58, 95% CI: 1.08–2.27). After adjusting for different covariates, a statistically significant association was observed only between low‐stable trajectory trajectories and GDM.

Conclusions

This study highlights a relationship between UIC and the risk of GDM. To better prevent iodine deficiency and GDM, persistent sufficient iodine status from pregnancy to delivery, should be emphasized.