Automated detection of nine infantile fundus diseases and conditions in retinal images using a deep learning system.

Purpose: We developed an Infant Retinal Intelligent Diagnosis System (IRIDS), an automated system to aid early diagnosis and monitoring of infantile fundus diseases and health conditions to satisfy urgent needs of ophthalmologists. Methods: We developed IRIDS by combining convolutional neural networks and transformer structures, using a dataset of 7697 retinal images (1089 infants) from four hospitals. It identifies nine fundus diseases and conditions, namely, retinopathy of prematurity (ROP) (mild ROP, moderate ROP, and severe ROP), retinoblastoma (RB), retinitis pigmentosa (RP), Coats disease, coloboma of the choroid, congenital retinal fold (CRF), and normal. IRIDS also includes depth attention modules, ResNet-18 (Res-18), and Multi-Axis Vision Transformer (MaxViT). Performance was compared to that of ophthalmologists using 450 retinal images. The IRIDS employed a five-fold cross-validation approach to generate the classification results. Results: Several baseline models achieved the following metrics: accuracy, precision, recall, F1-score (F1), kappa, and area under the receiver operating characteristic curve (AUC) with best values of 94.62% (95% CI, 94.34%-94.90%), 94.07% (95% CI, 93.32%-94.82%), 90.56% (95% CI, 88.64%-92.48%), 92.34% (95% CI, 91.87%-92.81%), 91.15% (95% CI, 90.37%-91.93%), and 99.08% (95% CI, 99.07%-99.09%), respectively. In comparison, IRIDS showed promising results compared to ophthalmologists, demonstrating an average accuracy, precision, recall, F1, kappa, and AUC of 96.45% (95% CI, 96.37%-96.53%), 95.86% (95% CI, 94.56%-97.16%), 94.37% (95% CI, 93.95%-94.79%), 95.03% (95% CI, 94.45%-95.61%), 94.43% (95% CI, 93.96%-94.90%), and 99.51% (95% CI, 99.51%-99.51%), respectively, in multi-label classification on the test dataset, utilizing the Res-18 and MaxViT models. These results suggest that, particularly in terms of AUC, IRIDS achieved performance that warrants further investigation for the detection of retinal abnormalities. Conclusions: IRIDS identifies nine infantile fundus diseases and conditions accurately. It may aid non-ophthalmologist personnel in underserved areas in infantile fundus disease screening. Thus, preventing severe complications. The IRIDS serves as an example of artificial intelligence integration into ophthalmology to achieve better outcomes in predictive, preventive, and personalized medicine (PPPM / 3PM) in the treatment of infantile fundus diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00350-y.

Morphological Rule-Constrained Object Detection of Key Structures in Infant Fundus Image.

The detection of optic disc and macula is an essential step for ROP (Retinopathy of prematurity) zone segmentation and disease diagnosis. This paper aims to enhance deep learning-based object detection with domain-specific morphological rules. Based on the fundus morphology, we define five morphological rules, i.e., number restriction (maximum number of optic disc and macula is one), size restriction (e.g., optic disc width: 1.05 +/- 0.13 mm), distance restriction (distance between the optic disc and macula/fovea: 4.4 +/- 0.4 mm), angle/slope restriction (optic disc and macula should roughly be positioned in the same horizontal line), position restriction (In OD, the macula is on the left side of the optic disc; vice versa for OS). A case study on 2953 infant fundus images (with 2935 optic disc instances and 2892 macula instances) proves the effectiveness of the proposed method. Without the morphological rules, naïve object detection accuracies of optic disc and macula are 0.955 and 0.719, respectively. With the proposed method, false-positive ROIs (region of interest) are further ruled out, and the accuracy of the macula is raised to 0.811. The IoU (intersection over union) and RCE (relative center error) metrics are also improved.

Association of Paracentral Acute Middle Maculopathy with Visual Prognosis in Retinal Artery Occlusion: A Retrospective Cohort Study.

Background: The association between paracentral acute middle maculopathy (PAMM) and visual acuity in patients with retinal artery occlusion (RAO) is unknown. This study explored the clinical features and prognostic factors for visual acuity of RAO accompanied by PAMM. Methods: This retrospective study included patients with RAO who underwent FFA and OCT examinations at Shenzhen Eye Hospital from July 2015 to June 2019. The changes in vision and macular structure were observed. Results: Eighty-eight patients were included. There were 58 patients (65.9%) with central RAO (CRAO) and 30 (34.1%) with branch RAO (BRAO). Fifty-two eyes were diagnosed with PAMM, of which 33 eyes (63.5%) were from CRAO patients and 19 (36.5%) were from BRAO patients. At diagnosis, the PAMM group had significantly better logMAR BCVA values than the no-PAMM group (median (IQR), 1.35 (0.725-2) vs. 2.15 (1.47-2.3), P=0.002). In addition, the PAMM group had significantly better logMAR BCVA values during follow-up than the no-PAMM group (median (IQR), 1 (0.05-2) vs. 2 (1.15-2.3), P=0.001). After adjustment for age, gender, CRAO/BRAO, comorbidities, and symptom duration, PAMM was associated with good visual acuity improvement (RR = 3.29, 95% CI: 1.29-8.37, P=0.013). Conclusion: PAMM was associated with good visual acuity improvement during follow-up in patients with RAO.

Refractive and biometrical characteristics of children with retinopathy of prematurity who received laser photocoagulation or intravitreal ranibizumab injection.

PURPOSE: To investigate the refractive and biometrical developments of children with retinopathy of prematurity (ROP) who received laser photocoagulation (LP) or intravitreal ranibizumab injection as treatment. METHODS: This case-control study involved cases with Zone II Stage 3 ROP. Fourteen children (28 eyes) who received single LP were included in the laser group, and 14 children (27 eyes) who received single intravitreal ranibizumab injection were included in the injection group. The mean age at operation was 37.00±1.72 and 36.36±1.66 weeks for the laser and injection groups, respectively (P=0.161), and refraction measurements and biometry were performed at the mean age of 5.00±1.63 and 5.00±0.94 years for the laser and injection groups, respectively (P=1.000). Spherical equivalent (SE) after mydriatic refraction and best corrected visual acuity (BCVA) were measured by refraction test. Central corneal thickness (CCT), anterior corneal surface curvature and curvature radius, anterior chamber depth (ACD), lens thickness (LT) and axial length (AL) were measured by biometry using the IOL Master700 biometric instrument (Carl Zeiss Meditec AG). The biometrical images were reanalysed using a self-developed program in MATLAB (R2016a, MathWorks, Inc.) to obtain additional eye parameters, including the curvatures of the posterior cornea and the anterior and posterior surfaces of the lens. SPSS (V.23.0) was used for statistical analysis. Independent sample t test was used to compare the eyeball biological and refractive state measures of the two groups, and Pearson correlation coefficient was used to evaluate the correlation between SE and the biological parameters. RESULTS: 1. (1) Cornea-related parameters: CCT (0.54±0.04mm vs 0.55±0.02mm, P>0.05), anterior corneal surface curvature radius (7.56±0.26 mm vs 7.67±0.43mm, P>0.05) and posterior corneal surface curvature radius (6.82±0.27mm vs 6.79±0.42mm, P>0.05). (2) ACD (3.21 ± 0.25mm vs 3.22 ± 0.19mm, P>0.05). (3) Lens-related parameters: anterior lens surface curvature radius (10.04±0.89mm vs 9.82±1.08mm, P>0.05), posterior lens surface curvature radius (5.49±0.55mm vs 5.92±0.73mm, P<0.05) and LT (3.80±0.14mm vs 3.59±0.16mm, P<0.05). (4) AL (21.82±1.07 vs 22.68±1.61, P<0.05). (5) Parameters related to refractive state: SE (-2.43±3.56 vs -0.53±3.12, P<0.05) and BCVA (log MAR, 0.17±0.14 vs 0.21±0.18, P>0.05). 2. (1) The SE of children in the laser group was positively correlated with LT (r=0.438, P<0.05), negatively correlated with ACD (r=-0.437, P<0.05) and had no significant correlation with other eyeball biological indicators (P>0.05). (2) The SE of children in the injection group was negatively correlated with AL (r=-0.537, P<0.05), positively correlated with CCT (r=0.455, P<0.05) and had no significant correlation with other eyeball biological indicators (P>0.05). CONCLUSION: LP and intravitreal ranibizumab injection as ROP treatments produce myopic refraction with increased degree of myopia in children who received LP than in children who received ranibizumab injection. The increased myopia after LP is due to the increases in LT and posterior lens curvature and a shallow ACD.

The Perceptions and Experiences of Mobile Health Technology by Older People in Guangzhou, China: A Qualitative Study.

The study explores older people's perceptions and experiences with mobile technology adoption in hospitals. Twenty nine older people were interviewed at a tertiary hospital in Guangzhou from June to December 2020. All the interviews were analyzed using thematic analysis. Older people are a diversified group. Various factors impact their readiness for technology use, including their educational level, age, past experiences, living arrangements, etc. The older people in this study in general expressed a great concern about using the new health technology and many encountered barriers to its successful adoption. Yet, the barriers and difficulties that they encountered are embedded in a changed social context in China. The findings above provide insights into the adoption of health technology, and tailored measures to facilitate older people's technology adoption are suggested.

Study of the Biological Developmental Characteristics of the Eye in Children After Laser Surgery for the Treatment of Retinopathy of Prematurity.

OBJECTIVE: To observe the differences in ocular biology between premature infants who had undergone retinal laser photocoagulation (LP) for retinopathy of prematurity (ROP) and full-term infants and to investigate the relationships between these differences and the development of the refractive state. METHODS: This retrospective, cross-sectional study included 25 children (50 eyes) who had undergone laser treatment for aggressive posterior retinopathy of prematurity (AP-ROP), ROP in zone I requiring treatment, or ROP in zone II requiring treatment in the posterior pole (laser group) and 29 full-term infants (58 eyes) who had not (control group). Basic information, spherical equivalent (SE), and best corrected visual acuity (BCVA) were collected from the two groups. Their mean ages were 7.32 ± 2.85 and 7.34 ± 2.57 years, respectively (t = -0.047, P = 0.96). Ocular biology data were measured using an IOL Master 700 instrument (Carl Zeiss Meditec AG) and the data were processed using MATLAB (R2016a, Mathworks Inc.). The data markers included central corneal thickness (CCT), anterior and posterior surface corneal curvature radius (CCR), anterior chamber depth (ACD), lens thickness (LT), lens anterior surface curvature radius, lens posterior surface curvature radius, and eye axis length (AL). Optometric data were collected simultaneously and all BCVA values were converted to the logarithm of the minimum angle of resolution (LogMAR) for analysis. The data were statistically analyzed using SPSS software (V.23.0). Independent sample t-tests were used for the assessment of ocular biology and refractive indices in both groups of children and Pearson correlation coefficients were used to evaluate the correlations between age, gestational age at birth and ocular biology structural parameters. P < 0.05 was considered statistically significant. RESULTS: Comparisons of ocular biomarkers, refractive status, and BCVA between children in the laser and control groups showed relationships among ocular biomarkers, including the corneal-related parameters of CCT (0.54 ± 0.04 mm and 0.56 ± 0.03 mm, t = -2.116, P < 0.05), anterior surface CCR (7.53 ± 0.33 mm and 7.84 ± 0.30 mm, t = -5.063, P < 0.05), posterior surface CCR (6.75 ± 0.34 mm and 7.03 ± 0.24 mm, t = -4.864, P < 0.05); as well as those related to anterior chamber depth (ACD) were 3.24 ± 0.26 mm and 3.64 ± 0.26 mm, respectively (t = -8.065, P < 0.05), lens-related parameters (LT) were 3.80 ± 0.19 mm and 3.45 ± 0.16 mm, respectively (t = 10.514, P < 0.05); anterior lens surface curvature radius were 10.02 ± 0.93 mm and 10.52 ± 0.85 mm, respectively (t = -2.962, P < 0.05); posterior lens surface curvature radius were 5.55 ± 0.51 mm and 5.80 ± 0.36 mm, respectively (t = -2.917, P < 0.05), and ocular axis (AL) were 22.60 ± 1.42 mm and 23.45 ± 1.23 mm, respectively (t = -3.332, P < 0.05). Moreover, comparison of refractive status and BCVA between two groups of children showed an SE of -1.23 ± 3.38 D and -0.07 ± 2.00 D (t = -2.206, P < 0.05) and LogMAR (BCVA) of 0.12 ± 0.13 and 0.05 ± 0.11 (t = 3.070, P < 0.05). Analysis of the correlations between age and ocular biomarkers and refractive status of children in the laser and control groups showed correlations between age and ocular biomarkers in the two groups, in which age in the laser group was positively correlated with AL (r = 0.625, P < 0.05) but not with other biomarkers (P > 0.05). Age in the control group was negatively correlated with CCT, ACD, and AL (r = 0.303, 0.468, 0.703, P < 0.05), as well as with LT (r = -0.555, P < 0.05), with no correlation with other biomarkers (P > 0.05). Analysis of the correlation between age and refractive status of children in both groups showed that the age of children in both laser and control groups was negatively correlated with SE (r = -0.528, -0.655, P < 0.05) and LogMAR (BCVA) (r = -0.538, -0.542, P < 0.05). Analysis of the correlations between refractive status and ocular biomarkers in children in the laser and control groups showed that the refractive status in children in the laser group was negatively correlated with AL (r = -0.773, P < 0.05) but not with other biomarkers in this group (P > 0.05). The refractive status of children in the control group was negatively correlated with ACD and AL (r = -0.469, -0.734, P < 0.05), positively correlated with LT (r = 0.364, P < 0.05), and was not correlated with other biomarkers in this group (P > 0.05). Analysis of the correlations of gestational age at birth with ocular biomarkers and refractive status in children in the laser group showed a positive correlation between gestational age at birth and AL (r = 0.435, P < 0.05) but no other correlations with the other biomarkers (P > 0.05). Moreover, gestational age at birth was negatively correlated with SE (r = -0.334, P < 0.05) and LogMAR (BCVA) (r = -0.307, P < 0.05) in children in the laser group. CONCLUSIONS: Compared to full-term infants, the development of CCT, ACD, LT, and AL was relatively delayed after ROP laser surgery, resulting in thin central corneal thickness, steep corneas, shallow anterior chambers, thicker lenses, "rounder" lens morphology, increased refractive power, and short eye axes, leading to the development of myopia. The changes in refractive status were mainly influenced by increased lens thickness. The results of this study showed that the lower the gestational age at birth, the greater the effects on emmetropization in children after ROP, and the more likely the development of myopia.

Clinical and Optical Coherence Tomography Angiographic Features in Patients with Postcataract Stenotrophomonas maltophilia Endophthalmitis.

PURPOSE: To report the clinical presentations and optical coherence tomography (OCT) angiographic features of patients with postcataract surgery endophthalmitis due to Stenotrophomonas maltophilia. Methods. A retrospective observational study of 4 patients who developed S. maltophilia endophthalmitis after cataract surgery. Pars plana vitrectomy (PPV) was performed to control the infection. Patients were followed up for six months. Complete ophthalmological examination results were collected before and after PPV. RESULTS: Patients' response to PPV therapy was excellent and the infection was cured in all cases. OCTA showed that, at the one-month follow-up, the vascular density (VD) and perfusion density (PD) in the superficial capillary plexus (SCP) were significantly lower than those in healthy collateral eyes. As time went on, the SCP-VD and SCP-PD values gradually improved. CONCLUSIONS: With early PPV, the infection caused by S. maltophilia can be cured. OCTA provides a quantitative noninvasive assessment to evaluate the severity and prognosis of patients with S. maltophilia endophthalmitis.

Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease.

PURPOSE: To report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19). PARTICIPANT AND METHODS: A 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated. RESULTS: Slit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value: 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2. CONCLUSION: SARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva.

Characterization of the gut microbiota in frail elderly patients.

BACKGROUND: The change in the composition of gut microbiota has been reported in the elderly and in the frail individuals; however, studies on gut microbiota in frail elderly are limited. AIMS: This study aimed to investigate the gut microbiota of the frail elderly. METHODS: From September 2017 to February 2018, 27 elderly patients hospitalized in the Department of Geriatrics of our hospital were enrolled and divided into the frailty group (n = 15) and the control group (n = 12) based on the cutoff of 0.25 for the frailty index. The fecal samples were collected for 16S rRNA-amplicon sequencing to analyze the composition and richness of gut microbiota. Operational taxonomic unit (OTU) clustering was performed using Usearch software. Intra-sample diversity (alpha-diversity) analysis and inter-sample diversity (beta-diversity) analyses were performed. The community richness was compared between the two groups at family and genus levels. RESULTS: There were 1903 and 1880 OTUs identified in the control and frailty groups, respectively, with 1282 OTUs overlap between the two groups. The alpha diversity of microbiota community was similar between the two groups, whereas the frailty group had larger beta diversity than the control group. The top-10 taxonomy categories and abundances of gut microbiota between the two groups were similar. As for the gut microbiota composition, 4 families and 17 genera were significantly different between the two groups (p < 0.05). CONCLUSION: These results suggested that frailty can affect gut microbiota diversity and compositions in late elderly hospitalized patients.

A Novel Mutation in the NDP Gene is Associated with Familial Exudative Vitreoretinopathy in a Southern Chinese Family.

Aims: To report a clinical and genetic investigation of a southern Chinese family with X-linked recessive exudative vitreoretinopathy and vitreous hemorrhage. Materials and Methods: We collected clinical data from a proband and his family. Complete ophthalmic examinations were carried out on the proband. Genomic DNA was sampled from either peripheral blood or buccal swabs of 13 individuals, and whole exome sequencing was performed on the proband and his parents. Sanger sequencing was utilized to validate the probable mutation in the proband and the remaining family members. Results: Seventeen family members, with three affected individuals were included in this study. The predominant phenotypes, with highly variable expressivity, were vitreoretinopathy, vitreous hemorrhage, retinal detachment, and even phthisis. A Y53C mutation in the NDP gene (HGNC:7678; NM_000266.3:exon2:c.A158G:p.Y53C;NP_000257.1:p.Tyr53Cys) was identified as being the most probable pathogenic mutation. Co-segregation of the mutation with the variable phenotype was confirmed within the proband's family. Conclusions: The clinical appearance of familial exudative vitreoretinopathy was highly variable, among the three affected male family members. A novel missense mutation in the NDP gene was identified as the pathogenic mutation.

COMPARISON OF INTRAVITREAL INJECTION OF RANIBIZUMAB VERSUS LASER THERAPY FOR ZONE II TREATMENT-REQUIRING RETINOPATHY OF PREMATURITY.

PURPOSE: To compare the efficacy of intravitreal injection of ranibizumab (IVR) monotherapy and laser therapy for treatment-requiring retinopathy of prematurity (ROP) in Zone II. METHODS: A prospective, randomized, controlled single-center trial was applied from January 2014 to December 2014; infants who were diagnosed as Zone II treatment-requiring ROP (i.e., Zone II Stage 2 or 3 ROP with plus disease) were randomly assigned to receive IVR monotherapy or laser therapy, and the follow-up interval was at least 6 months. Any eyes that developed recurrence of ROP underwent crossover re-treatment. RESULTS: A total of 100 eyes of 50 ethnic Han Chinese infants were enrolled. At the last follow-up, 26 eyes of 13 infants developed recurrence of ROP in the IVR group and 2 eyes of 1 infant developed recurrence of ROP in the laser therapy group. There was a significant statistical difference in the rate of ROP recurrence between IVR and laser therapy to treat Zone II treatment-requiring ROP (P = 0.001). CONCLUSION: Although IVR appears to regress ROP to certain levels and continue to promote the vascularization of peripheral retinal vessels, a substantial proportion of infants developed recurrence of ROP after a single-dose IVR. Therefore, IVR is not recommended as a single-dose monotherapy for Zone II treatment-requiring ROP.

The small-molecule compound BM-1197 inhibits the antiapoptotic regulators Bcl-2/Bcl-xL and triggers apoptotic cell death in human colorectal cancer cells.

Small molecule BH3 mimetics comprise a promising new chemotherapeutic strategy for treating relapsed or chemoresistant cancer. In this study, we investigated the cellular mechanism of action by which BM-1197, a Bcl-xL/Bcl-2 dual inhibitor, triggers apoptosis in a panel of colorectal cancer (CRC) lines. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, we determined that BM-1197 inhibited CRC cell growth in a concentration- and time-dependent manner. The 50 % inhibitory concentration (IC50) values for the most sensitive cell lines, SW620 and SW480, ranged from 0.07 to 1.10 µM in response to a 72-h treatment. In CRC cells, BM-1197 induced apoptotic death without affecting the expression of Bcl-2 family proteins. However, BM-1197 effectively triggered a conformational change in Bax, releasing Bim from Bcl-xL by disrupting the interaction between Bcl-xL and Bak/Bax. Compared with the control group, BM-1197 treatment significantly increased the fraction of SW480 cells in the sub-G1 phase, the apoptosis rate, and cellular internucleosomal DNA fragmentation. The proapoptotic activity was associated with cytochrome c release, caspase-3 activation, and PARP-1 cleavage. Collectively, BM-1197 effectively suppressed the growth of the human CRC cell line SW480 by inducing mitochondria-dependent apoptotic cell death. These data have specific implications for the in vivo analysis and clinical evaluation of BM-1197 in CRC.