Artificial intelligence-aided diagnosis and treatment in the field of optometry.

With the rapid development of computer technology, the application of artificial intelligence (AI) to ophthalmology has gained prominence in modern medicine. As modern optometry is closely related to ophthalmology, AI research on optometry has also increased. This review summarizes current AI research and technologies used for diagnosis in optometry, related to myopia, strabismus, amblyopia, optical glasses, contact lenses, and other aspects. The aim is to identify mature AI models that are suitable for research on optometry and potential algorithms that may be used in future clinical practice.

Srgap2 suppression ameliorates retinal ganglion cell degeneration in mice.

Slit-Robo GTPase-activating protein 2 (SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout (Srgap2+/-) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes (Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/- mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.

Artificial intelligence-assisted diagnosis of ocular surface diseases.

With the rapid development of computer technology, the application of artificial intelligence (AI) in ophthalmology research has gained prominence in modern medicine. Artificial intelligence-related research in ophthalmology previously focused on the screening and diagnosis of fundus diseases, particularly diabetic retinopathy, age-related macular degeneration, and glaucoma. Since fundus images are relatively fixed, their standards are easy to unify. Artificial intelligence research related to ocular surface diseases has also increased. The main issue with research on ocular surface diseases is that the images involved are complex, with many modalities. Therefore, this review aims to summarize current artificial intelligence research and technologies used to diagnose ocular surface diseases such as pterygium, keratoconus, infectious keratitis, and dry eye to identify mature artificial intelligence models that are suitable for research of ocular surface diseases and potential algorithms that may be used in the future.

Meibomian gland morphological changes in ocular herpes zoster patients based on AI analysis.

Varicella-zoster virus (VZV) infections result in a series of ophthalmic complications. Clinically, we also discover that the proportion of dry eye symptoms was significantly higher in patients with herpes zoster ophthalmicus (HZO) than in healthy individuals. Meibomian gland dysfunction (MGD) is one of the main reasons for dry eye. Therefore, we hypothesize that HZO may associate with MGD, affecting the morphology of meibomian gland (MG) because of immune response and inflammation. The purpose of this study is to retrospectively analyze the effect of HZO with craniofacial herpes zoster on dry eye and MG morphology based on an Artificial intelligence (AI) MG morphology analytic system. In this study, 26 patients were diagnosed as HZO based on a history of craniofacial herpes zoster accompanied by abnormal ocular signs. We found that the average height of all MGs of the upper eyelid and both eyelids were significantly lower in the research group than in the normal control group (p < 0.05 for all). The average width and tortuosity of all MGs for both upper and lower eyelids were not significantly different between the two groups. The MG density of the upper eyelid and both eyelids were significantly lower in the HZO group than in the normal control group (p = 0.020 and p = 0.022). Therefore, HZO may lead to dry eye, coupled with the morphological changes of MGs, mainly including a reduction in MG density and height. Moreover, it is important to control HZO early and timely, which could prevent potential long-term severe ocular surface injury.

Uneven Meibomian Gland Dropout in Patients with Meibomian Gland Dysfunction and Demodex Infestation.

The purpose of this study was to compare the differences between uneven meibomian gland (MG) atrophy with and without Demodex infestation based on the index of uneven atrophy score (UAS). In this retrospective cohort study, 158 subjects were recruited, including 66 subjects in the Demodex-positive MGD group, 49 subjects in the Demodex-negative MGD group, and 43 subjects as normal control. No significant difference was verified in OSDI, TMH, TBUT, CFS, lid margin score, and meibograde (all p > 0.05) between the Demodex-positive MGD group and the Demodex-negative MGD group. The UAS index of the upper eyelid or both eyelids was significantly higher in the Demodex-positive group in comparison with the normal control group and Demodex-negative group and the difference was statistically significant between the three groups. The UAS was significantly positive correlation with OSDI (r = 0.209, p < 0.05), lid margin score (r = 0.287, p < 0.001), and meibograde (r = 0.356, p < 0.001), which has a significant negative correlation with TBUT (r = −0.248, p < 0.05). Thus, Demodex infestation can cause uneven MG atrophy and we propose a novel index of UAS, which is used to evaluate uneven atrophy of MGs and as a morphological index of Demodex infestation.

Metagenomic profiling of ocular surface microbiome changes in Demodex blepharitis patients.

Purpose: To compare the ocular surface and meibum microbial communities of humans with Demodex Blepharitis (DB) and healthy controls. Methods: Conjunctival sac and meibum samples from 25 DB patients and 11 healthy controls were analyzed using metagenomic next-generation sequencing (mNGS). Results: The alpha-diversity of the conjunctival sac microbiome of the DB group (observed, Chao1, ACE) was lower than that of the control group, whereas all meibum diversity indicators were similar. In conjunctival samples, the relative abundance (RA) of the phylum Proteobacteria was significantly higher (p=0.023), and the RA of both phyla Actinobacteria and Firmicutes was significantly lower (p=0.002, 0.025, respectively) in the DB group than that in the control group. In meibum samples, the RA of the phyla Proteobacteria and Actinobacteria were similar, whereas that of the phylum Firmicutes was significantly lower in the DB group (p=0.019) than that in the control group. Linear discriminant analysis with effect size measurement of the conjunctival and meibum microbiomes showed that Sphingobium sp. YG1 and Acinetobacter guillouiae were enriched in the DB group. Sphingobium sp. YG1, Acinetobacter guillouiae and Pseudomonas putida in the DB group were related to more severe ocular surface clinical parameters. Discriminative genera's principal coordinate analysis separated all control and DB microbiomes into two distinct clusters. Conclusions: Proteobacteria's increased prevalence may indicate ocular microbial community instability. The species Sphingobium sp. YG1 and Acinetobacter guillouiae are potentially pathogenic bacterial biomarkers in DB. Demodex infection mainly affects the ocular surface microbiome rather than penetrating deeper into the meibomian gland.

Uneven Index: A Digital Biomarker to Prompt Demodex Blepharitis Based on Deep Learning.

Purpose: To evaluate ocular surface manifestations and morphological changes in meibomian glands (MGs) based on artificial intelligence (AI) analysis in patients with Demodex blepharitis. Methods: In this retrospective study, 115 subjects were enrolled, including 64 subjects with Demodex blepharitis and 51 subjects without Demodex blepharitis as control group. Morphological indexes were evaluated for height, width, tortuosity, MG density, total variation, and the three types of corrected total variation as Uneven indexes. Results: There were no statistically significant differences in all MGs' average tortuosity and width between the two groups. The average height of all MGs and MG density were significantly lower in the Demodex blepharitis group than control group. The total variation and two types of Uneven indexes were significantly higher in the Demodex blepharitis group than in the control group. Especially the Uneven Index of total variation/MG density had an AUC of 0.822. And the sensitivity and specificity were 59.4% and 92.2%, respectively, at a cut-off value of 3971.667. In addition, Demodex blepharitis was associated with significantly lower meibum quality and expressibility, severe atrophy of MGs, a higher ocular surface disease index (OSDI), and more instability of the tear film. Conclusion: Demodex mites are strongly associated with morphological changes in the MGs and may cause uneven gland atrophy. Therefore, the novel characteristic parameter, the Uneven index, may serve as a digital biomarker to evaluate uneven atrophy of MGs and prompt Demodex blepharitis.

Meibomian Gland Density: An Effective Evaluation Index of Meibomian Gland Dysfunction Based on Deep Learning and Transfer Learning.

We aimed to establish an artificial intelligence (AI) system based on deep learning and transfer learning for meibomian gland (MG) segmentation and evaluate the efficacy of MG density in the diagnosis of MG dysfunction (MGD). First, 85 eyes of 85 subjects were enrolled for AI system-based evaluation effectiveness testing. Then, from 2420 randomly selected subjects, 4006 meibography images (1620 upper eyelids and 2386 lower eyelids) graded by three experts according to the meiboscore were analyzed for MG density using the AI system. The updated AI system achieved 92% accuracy (intersection over union, IoU) and 100% repeatability in MG segmentation after 4 h of training. The processing time for each meibography was 100 ms. We discovered a significant and linear correlation between MG density and ocular surface disease index questionnaire (OSDI), tear break-up time (TBUT), lid margin score, meiboscore, and meibum expressibility score (all p < 0.05). The area under the curve (AUC) was 0.900 for MG density in the total eyelids. The sensitivity and specificity were 88% and 81%, respectively, at a cutoff value of 0.275. MG density is an effective index for MGD, particularly supported by the AI system, which could replace the meiboscore, significantly improve the accuracy of meibography analysis, reduce the analysis time and doctors' workload, and improve the diagnostic efficiency.

Glaucoma and risk factors three years after congenital cataract surgery.

BACKGROUND: This study aimed to identify the incidence of and risk factors for postoperative glaucoma-related adverse events at various time points after congenital cataract surgery. METHODS: This retrospective cohort study enrolled 259 eyes from 174 patients (surgical age ≤ 7 years) who underwent congenital cataract surgery. All surgical procedures were conducted at the Eye Hospital of Wenzhou Medical University between May 2011 and March 2019. Patients were classified into group 1 [primary intraocular lens (IOL) implantation, N = 111 eyes], group 2 (secondary IOL implantation, N = 85 eyes), and group 3 (no IOL implantation, N = 63 eyes). We recorded demographic factors and incidence and risk factors for glaucoma-related adverse events. RESULTS: Glaucoma-related adverse events occurred in 21 (8.1%) eyes, whereas 27 (10.4%) eyes developed steroid-induced ocular hypertension. The percentage of glaucoma-related adverse events was 0%, 1.2%, 1.2%, 1.6%, 4.0%, and 8.9% at 1 month, 6 months, 1 year, 2 years, 3 years and 4 years after surgery, respectively. Sixteen (18.8%), five (7.9%), and zero eyes developed glaucoma-related adverse events in groups 2, 3, and 1, respectively. Family history of congenital cataract [hazard ratio (HR), 50.463; 95% confidence interval (CI), 7.051-361.139; P < 0.001], preoperative central corneal thickness (CCT) [HR, 1.021; 95% CI, 1.009-1.034; P = 0.001], preoperative horizontal corneal diameter (HCD) [HR, 3.922; 95% CI, 1.558-9.804; P = 0.004], and preoperative lens thickness (LT) [HR, 3.745; 95% CI, 1.344-10.417; P = 0.012] were identified as predictors of postoperative glaucoma-related adverse events. CONCLUSIONS: Family history of congenital cataract, thicker preoperative CCT, smaller preoperative HCD, and thinner preoperative LT are the main risk factors of postoperative glaucoma-related adverse events. Regular monitoring of children after cataract surgery with these risk factors may help ophthalmologists detect susceptible individuals and provide timely interventions in the clinic.

Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors.

A class of imidazoisoindole (III) heme-binding indoleamine-2,3-dioxygenase (IDO1) inhibitors were optimized via structure-based drug design into a series of tryptophan-2,3-dioxygenase (TDO)-selective inhibitors. Kynurenine pathway modulation was demonstrated in vivo, which enabled evaluation of TDO as a potential cancer immunotherapy target. As means of mitigating the risk of drug-drug interactions arising from cytochrome P450 inhibition, a novel property-based drug design parameter, herein referred to as the CYP Index, was implemented for the design of inhibitors with appreciable selectivity for TDO over CYP3A4. We anticipate the CYP Index will be a valuable design parameter for optimizing CYP inhibition of any small molecule inhibitor containing a Lewis basic motif capable of binding heme.

S100A8 promotes migration and infiltration of inflammatory cells in acute anterior uveitis.

Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined the role of S100A8-positive cells in acute anterior uveitis (AAU) and keratitis. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 levels in leukocytes, but reduced its presence significantly in the iris-ciliary body after LPS injection. Moreover, inhibition of NF-kB activation remarkably suppressed both progression of AAU and total S100A8 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 protein level was also found to be elevated in the serum of AAU patients parallel with the progression of AAU through the designated clinical stages. Thus, S100A8 plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8-positive cells. Our findings suggest that serum levels of S100A8 protein can be used to monitor inflammatory activity in AAU.

[Interaction Between Occupational Vanadium Exposure and hsp70-hom on Neurobehavioral Function].

OBJECTIVE: In determine the effect of heat shock protein 70-hom gene (hsp70-hom) polymorphism on the neurobehavioral function of workers exposed to vanadium. METHODS: Workers from the vanadium products and chemical industry were recruited by cluster sampling. Demographic data and exposure information were collected using a questionnaire. Neurobehavioral function was assessed by Neurobehavioral Core Test Battery. The hsp70-hom genotype was detected by restricted fragment length polymorphism-polymerase chain reaction (RFLP-PCR). A neurobehavioral index (NBI) was formulated through principal component analysis. RESULTS: Workers with a T/C genotype had worse performance in average reaction time, visual retention, digital span (backward), Santa Ana aiming (non-habitual hand), pursuit aiming (right points, total points), digit symbol and NBI score than others (P < 0.05). The relative risk of abnormal NBI score of the workers with a T/C genotype was 1.748 fold of those with a T/T genotype. The relative risk of abnormal.NBI score of the workers exposed to vanadium was 3.048 fold of controls (P < 0.05). But after adjustment with age and education, only vanadium exposure appeared with a significant effect on NBI score. When gene polymorphism and vanadium exposure coexisted, the effect of vanadium on neurobehavioral function was attenuated, but the influence of T/C genotype increased Codds ratio (OR = 4.577, P < 0.05). After adjustment with age and education, the OR of T/C genotype further increased to 7.777 (P < 0.05). Vanadium exposure and T/C genotype had.a bio-interaction effect on NBI score Crelative excess risk due to interaction (RERI) = 4.12, attributable proportion (AP) = 0.7, synergy index (S) = 6.45]. After adjustment with age and education, the RERI became 2.49 and the AP became 0.75, but no coefficient of interaction was produced. CONCLUSION: Priorities of occupational protection should be given to vanadium-exposed workers with a hsp70-hom T/C genotype and low education level.

[Oxidative Stress Level of Vanadium-exposed Workers].

OBJECTIVE: To determine the oxidative stress level in peripheral blood of vanadium-exposed workers, as an indication of population health effect of vanadium on human neurobehavioral system. METHODS: 86 vanadium-exposed workers and 65 non-exposed workers were recruited by cluster sampling. A questionnaire was administered to collect demographic and occupational exposure information. Serum activity of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS) and malonaldehyde (MDA) contents were detected by kit assay. The differences in oxidative stress level between vanadium-exposed and non-exposed workers were compared. RESULTS: Vanadium-exposed workers had higher levels of MDA contents than the controls. The total superoxide dismutase(T-SOD) activity in vanadium-exposed workers was significantly lower than that in the controls, which was associated with lowered levels of manganese superoxide dismutase (Mn-SOD) activity. No changes in serum levels of cupro-zinc superoxide dismutase (CuZn-SOD) was found in vanadium-exposed workers. No difference in iNOS activity was found between vanadium-exposed workers and controls. CONCLUSION: Vanadium exposure increases free radical production in serum and reduces antioxidant capacity. But the relationship between vanadium exposure and iNOS damage remains uncertain.

Asymmetric one-pot synthesis of 1,3-oxazolidines and 1,3-oxazinanes via hemiaminal intermediates.

A highly efficient method for the enantioselective one-pot synthesis of 1,3-oxazolidines and 1,3-oxazinanes has been reported. The reaction proceeds via the formation of hemiaminal intermediates obtained by the enantioselective addition of respective alcohols to imines catalyzed by a chiral magnesium phosphate catalyst, followed by intramolecular cyclization under mildly basic conditions. A wide range of substrates have been converted to the respective chiral heterocyclic products in high yields and with excellent enantioselectivities using this one-pot procedure.

Chiral calcium VAPOL phosphate mediated asymmetric chlorination and Michael reactions of 3-substituted oxindoles.

We disclose a novel high yielding and highly enantioselective chiral calcium VAPOL phosphate-catalyzed chlorination of 3-substituted oxindoles with N-chlorosuccinimide (NCS). The reaction conditions are also shown to be effective for the catalytic enantioselective Michael addition of 3-aryloxindoles to methyl vinyl ketone.

Prevalence of non-organ-specific autoantibodies in patients with pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening, organ-specific, autoimmune, blistering disease of the skin and mucous membranes. Although several reports suggest an association between pemphigus and other autoimmune connective tissue disorders, studies that measure non-organ-specific autoantibodies are lacking. OBJECTIVE: To evaluate the prevalence of antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies, and antibodies against extractable nuclear antigens (ENAs) in PV patients. METHODS: Serum samples were obtained from 59 PV patients and 50 healthy controls. Indirect immunofluorescence assays containing human epithelial cell substrates (HEp-2) and Crithidia luciliae were used to detect ANA and anti-dsDNA antibodies, respectively. A multiplexed addressable laser bead immunoassay was employed to measure autoantibodies to: Smith (Sm), ribonucleoprotein (RNP), Sjögren syndrome B (SSB/La), Sjögren syndrome A (SSA/Ro), histidyl transfer ribonucleic acid synthetase (Jo-1), topoisomerase I (Scl-70), and ribosome-P (Ribo-P) antigens. RESULTS: Positive ANAs were obtained in 22 of 59 (37.3%) PV patients compared with 4 of 50 (8.0%) healthy controls (p

A facile access to pyrroles from amino acids via an aza-Wacker cyclization.

A facile and efficient synthesis of pyrroles from readily available amino acids is described. The key step in the method is an aza-Wacker oxidative cyclization catalyzed by palladium(II)/Cu(OTf)2. A series of pyrroles were obtained by this method under mild conditions.