New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Research on classification method of high myopic maculopathy based on retinal fundus images and optimized ALFA-Mix active learning algorithm

AIM:To conduct a classification study of high myopic maculopathy(HMM)using limited datasets,including tessellated fundus,diffuse chorioretinal atrophy,patchy chorioretinal atrophy,and macular atrophy,and minimize annotation costs,and to optimize the ALFA-Mix active learning algorithm and apply it to HMM classification.METHODS:The optimized ALFA-Mix algorithm(ALFAMix+)was compared with five algorithms,including ALFA-Mix.Four models,including Res Net18,were established.Each algorithm was combined with four models for experiments on the HMM dataset.Each experiment consisted of 20 active learning rounds,with 100 images selected per round.The algorithm was evaluated by comparing the number of rounds in which ALFA-Mix+outperformed other algorithms.Finally,this study employed six models,including Efficient Former,to classify HMM.The best-performing model among these models was selected as the baseline model and combined with the ALFA-Mix+algorithm to achieve satisfactor y classification results with a small dataset.RESULTS:ALFA-Mix+outperforms other algorithms with an average superiority of 16.6,14.75,16.8,and 16.7 rounds in terms of accuracy,sensitivity,specificity,and Kappa value,respectively.This study conducted experiments on classifying HMM using several advanced deep learning models with a complete training set of 4252 images.The Efficient Former achieved the best results with an accuracy,sensitivity,specificity,and Kappa value of 0.8821,0.8334,0.9693,and 0.8339,respectively.Therefore,by combining ALFA-Mix+with Efficient Former,this study achieved results with an accuracy,sensitivity,specificity,and Kappa value of 0.8964,0.8643,0.9721,and 0.8537,respectively.CONCLUSION:The ALFA-Mix+algorithm reduces the required samples without compromising accuracy.Compared to other algorithms,ALFA-Mix+outperforms in more rounds of experiments.It effectively selects valuable samples compared to other algorithms.In HMM classification,combining ALFA-Mix+with Efficient Former enhances model performance,further demonstrating the effectiveness of ALFA-Mix+.

Visualized analysis of research on myopic traction maculopathy based on CiteSpace

AIM:To analyze the global scientific output concerning myopic traction maculopathy(MTM)and to summarize the research frontiers and hot topics of MTM related researches.METHODS:Data were collected for bibliometric and visualization analyses from Web of Science(WOS)Core Collection.Exported records were analyzed for titles,publication years,research institutions,journal names,authors,keywords,and abstracts using CiteSpace software version 6.1.RESULTS:A total of 839 related studies were analyzed,the publication volume increased annually,with Asia the most active region of MTM research.Optical coherence tomography angiography,optical coherence tomography,macular hole,high myopia,macular buckling were identified as the focus of the current research.Progression,association,classification and shape were identified as the major research frontiers.CONCLUSION:MTM is a major cause of visual loss in pathological myopic eyes.During the preceding 17y,the number of annual publications in MTM research increased gradually.Studies on the progression nature of MTM,genome-wide association study and proper classification of MTM might still be the frontiers of MTM researches.

A Semantic Adversarial Network for Detection and Classification of Myopic Maculopathy

The diagnosis of eye disease through deep learning (DL) technologyis the latest trend in the field of artificial intelligence (AI). Especially indiagnosing pathologic myopia (PM) lesions, the implementation of DL is adifficult task because of the classification complexity and definition system ofPM. However, it is possible to design an AI-based technique that can identifyPM automatically and help doctors make relevant decisions. To achieve thisobjective, it is important to have adequate resources such as a high-qualityPM image dataset and an expert team. The primary aim of this research isto design and train the DLs to automatically identify and classify PM intodifferent classes. In this article, we have developed a new class of DL models(SAN-FSL) for the segmentation and detection of PM through semanticadversarial networks (SAN) and few-short learning (FSL) methods, respectively.Compared to DL methods, the conventional segmentation methodsuse supervised learning models, so they (a) require a lot of data for trainingand (b) fixed weights are used after the completion of the training process.To solve such problems, the FSL technique was employed for model trainingwith few samples. The ability of FSL learning in UNet architectures is beingexplored, and to fine-tune the weights, a few new samples are being providedto the UNet. The outcomes show improvement in the detection area andclassification of PM stages. Betterment in the result is observed by sensitivity(SE) of 95%, specificity (SP) of 96%, and area under the receiver operatingcurve (AUC) of 98%, and the higher F1-score is achieved using 10-fold crossvalidation.Furthermore, the obtained results confirmed the superiority of theSAN-FSL method.

Diagnosis and treatment of myopic traction maculopathy

In recent years, the broad application of optical coherence tomography and vitrectomy, combined with research efforts in maculopathy in high myopia have provided many achievements, such as the new classification of myopic traction maculopathy (MTM). Here, we review the latest developments in the diagnosis and treatment of MTM, including its conception, clinical characteristics, pathogenesis, clinical stages, and the options for surgical treatment.

Dengue related maculopathy and foveolitis

A 24 year-old Malay lady presented with high grade fever,myalgia,generalized rashes,severe headache and was positive for dengue serology test.Her lowest platelet count was 45×10~9 cells/L.She complained of sudden onset of painlessness,profound loss of vision bilaterally 7 days after the onset of fever.On examination,her right eye best corrected vision was 6/30 and left eye was6/120.Her anterior segment examination was unremarkable.Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid.Systemic examination revealed normal findings except for residual petechial rashes.She was managed conservatively.Her vision improved tremendously after 2 months.The retinal hemorrhages and foveal elevation showed sign of resolving.Ocular manifestations following dengue fever is rare.However,bilateral visual loss can occur if both fovea arc involved.

Measurements of the parapapillary atrophy area and other fundus morphological features in high myopia with or without posterior staphyloma and myopic traction maculopathy

AIM:To investigate the affecting factors of parapapillary gamma and delta zones and other fundus morphological features in high myopia.METHODS:Seventy high myopia patients were included in this retrospective observational study and 47 patients were female.Patients were divided into three groups:no posterior staphyloma(no PS),PS with myopic traction maculopathy(PS with MTM),and PS without MTM using 3-dimensional magnetic resonance imaging and optical coherence tomography.MTM patients were fur ther classified into three types[epiretinal membrane,macular hole,and macular retinoschisis(MRS)].Diameters of the gamma and delta zones were measured among other morphometric variables using fundus photographs.RESULTS:Of the 70 individuals(127 eyes),the mean age was 57.46±13.56y.In univariate analysis,morphological features changed most dramatically in PS with MTM patients,who had the largest gamma zone diameters,the largest disk-fovea distance(DFD)and disk-fovea angle,and the smallest angle kappa and vertical distance of temporal arterial arcade.However,their horizontal delta zone diameter was smaller than in the patients with PS yet without MTM.In multivariate analysis,with axial length(AL)and age adjusted,the horizontal diameter in the delta zone of the PS without MTM group was still significantly larger than in the PS with MTM group(P=0.024).Comparing the three subtypes of MTM patients,the diameters of the gamma zone and DFD in MRS group were the largest.CONCLUSION:The characteristics of the gamma and delta zones change inconsistently in different stages of high myopia.These changes may be associated with anatomical changes caused by local traction.Factors such as PS,AL and age play an important role.These findings may provide a hint about the pathogenesis of traction in high myopia.

Age-related maculopathy susceptibility 2 participates in the phagocytosis functions of the retinal pigment epithelium

AIM: Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Many studies suggest that age-related maculopathy susceptibility 2 (ARMS2) is a second major susceptibility gene for AMD. At present, there is no functional information on this gene. Therefore, the purpose of the present study was to detect the expression of ARMS2 in retinal pigment epithelium (RPE) cells and to investigate the effect of ARMS2 on the phagocytosis function of RPE cells. METHODS: Immunofluorescence and reverse transcriptase PCR were used to demonstrate the presence and location of ARMS2 in ARPE-19 (human retinal pigment epithelial cell line, ATCC, catalog No.CRL-2302) cells. siRNA was used to knock down ARMS2 mRNA, and the effects of the knockdown on the phagocytosis function of the ARPE-19 cells were evaluated via Fluorescence Activated Cell Sorting (FACS). RESULTS: ARMS2 was present in ARPE-19 cells, localized in the cytosol of the perinuclear region. The expression of ARMS2 mRNA (messenger RNA) in ARPE-19 cells transfected with ARMS2-siRNA (small interfering RNA, 0.73+/- 0.08) was decreased compared with normal cells (1.00+/- 0.00) or with cells transfected with scrambled siRNA (0.95+/- 0.13) (P<0.05). After incubation of RPE cells with a latex beads medium for 12, 18, or 24 hours, the fluorescence intensities were 38.04 +/- 1.02, 68.92 +/- 0.92, and 78.00 +/- 0.12 in the ARMS2-siRNA-transfected groups, respectively, and 77.98 +/- 5.43, 94.87 +/- 0.60, and 98.30 +/- 0.11 in the scrambled siRNA-transfected groups, respectively. The fluorescent intensities of the same time points in the two groups were compared using Student's t-test, and the p values were all less than 0.001 at the three different time points. CONCLUSION: There is endogenous expression of ARMS2 in ARPE-19 cells. ARMS2 plays a role in the phagocytosis function of RPE cells, and this role may be one of the mechanisms that participates in the development of AMD.

Conjunctival flap advancement with or without scleral graft for hypotony maculopathy after trabeculectomy

AIM: To investigate the outcomes of adaptive conjunctival flap advancement surgical techniques with or without scleral graft for patients undergoing revision surgery after trabeculectomy.METHODS: This retrospective study included 28 eyes of 28 subjects from December 2015 to April 2018. A group of 15 eyes underwent conjunctival advancement only while the other 13 eyes did conjunctival advancement with partial thickness scleral graft. In both study groups, we considered the intraocular pressure(IOP) as our primary outcome and visual acuity(VA) as our secondary outcome. Both were assessed pre-and post-operatively till the last followup possible point. Additionally, we classified the patients according to complete and qualified success criteria.RESULTS: The mean age of the conjunctival advancement group was 36.87±19.25 y, while it was 44.08±18.04 in the other group. In both study groups, the mean IOP significantly increased after revision surgery at 1, 2, 3 mo and the last follow-up visit when compared to prior the surgery(P<0.001). Moreover, VA was significantly improved(P=0.03) in the final follow-up for both surgical techniques. When we compared the change from baseline in both groups, there was no significant difference between IOP improvement in 1 mo(P=0.263), while the difference was significant in 2 mo(P=0.03), 3 mo(P=0.02) and in the final follow-up visit postoperatively. However, this difference was not significant regarding VA(P=0.5).CONCLUSION: The both adaptive techniques of conjunctival advancement and conjunctival advancement with scleral graft are effective for treating patients with lateonset hypotony. Yet, more prospective studies are needed to assert upon these results.

A Novel Polymethyl Methacrylate (PMMA)-TiO_2 Nanocomposite and Its Thermal and Photic Stability

A new kind of polymethyl methacrylate （PMMA）-TiO2 nanocomposite was synthesized through polymerization. The thermal and photic stability of this PMMA TiO2 nanocomposites were investigated. The as prepared samples were characterized by scanning electron microscopy （SEM）, UV-Vis spectroscopy, differential thermal analysis （DTA） and the photo-induced weight loss, The results show that the photostability of the PMMA-TiO2 nanocomposite is higher than that of the pure PMMA under UV-light irradiation, The weight loss of the pure PMMA reaches 30 % after 300 h UVirradiation, while the composite only 0.3% under the identical experimental condition. The glass transition temperature （TR） of pure PMMA is only 80℃, while the Tg of the composite reaches 258℃. Compared with pure PMMA, the thermal stability of the composite is greatly enhanced.

Evolution of Diabetic Maculopathy from Marked Exudation to Subretinal Fibrosis: Clinical and Spectral Domain Optical Coherence Tomography Features

Diabetic maculopathy with marked exudation may lead to subretinal fibrosis. Two patients observed over multiple years evolved from macular exudation into subretinal fibrosis with severe visual loss. Spectral domain optical coherence tomography and color photographs document the clinical changes.

Optical Coherence Tomography Findings in a Case of Unilateral Acute Idiopathic Maculopathy

Purpose: To describe the clinical, angiographic, and Optical Coherence Tomography (OCT) findings in a patient with Unilateral Acute Idiopathic Maculopathy (UAIM) and to discuss a possible pattern of OCT findings in patients with this disease. Methods: Case report. Results: A 34-year-old man with UAIM was evaluated. During the acute phase fundus examination revealed a yellow thickening in the macular area of the right eye, Fluorescein Angiography (FA) showed early alternating patches of hypofluorescence and hyperfluorescence and late hyperfluorescence and OCT showed thickening of the outer retina in the foveal zone. Six weeks later, the macula had pigmentary mottling, FA showed an area of central hypofluorescence surrounded by a hyperfluorescent ring that remained unchanged during the angiogram and the OCT examination was normal. Conclusion: OCT is a useful diagnostic tool for UAIM. OCT evaluation of patients with this disease will exhibit the heterogeneous hyperreflectivity and thickening of the outer retina and Retinal Pigment Epithelium (RPE). A serous macular detachment may not be a prominent finding in UAIM.

Intraoperative optical coherence tomography findings during surgery for optic disc pit-associated maculopathy

Dear Editor,We report our experience using a continuous intraoperative optical coherence tomography(OCT)-enabled microscope system for real-time anatomical evaluation of the optic pit during surgery in an 8-year-old girl who presented with symptomatic optic disc pit(ODP) maculopathy. ODP is an extremely rare congenital anomaly secondary to colobomatous malformation of the optic nerve head, with a reported incidence of 0.00009%[1]. Although patients are frequently asymptomatic, approximately 40%-50% of patients experience visual symptoms because of subretinal fluid(SRF) accumulation beneath the macula.

Dengue Maculopathy: Case Series

We report a case series of dengue maculopathy with different ocular manifestations, managements, visual outcomes and sequelae of patients. All three cases were diagnosed to have dengue fever. Patients presented with symptoms of central scotoma (case 1 and case 3) and blurring of vision (case 2) on Day 9 of dengue fever. Fundus examination showed intra retinal haemorrhages (case 1 and case 2) and macula thickening (case 3). Optical coherence tomography (OCT) revealed macular thickening with intra retinal fluid (case 1) and diffuse retinal thickening (case 3), while in case 2, it had irregular ellipsoid line in OCT. Fundus fluorescence angiography (FFA) revealed parafoveal vasculitis. After treatment with systemic steroids, one patient had good visual outcome (case 2), while two others had a persistent central scotoma due to macula atrophy (case 3). Although it is a self limiting disease, but the mode of treatment is variable. Treatment with corticosteroids may hasten recovery of vision and prevent permanent visual impairment.

Predictive factors for photic phenomena after refractive,rotationally asymmetric,multifocal intraocular lens implantation

AIM： To investigate the independent factors associated with photic phenomena in patients implanted with refractive,rotationally asymmetric,multifocal intraocular lenses（MIOLs）.METHODS： Thirty-four eyes of 34 patients who underwent unilateral cataract surgery,followed by implantation of rotationally asymmetric MIOLs were included.Distance and near visual acuity outcomes,intraocular aberrations,preferred reading distances,preoperative and postoperative refractive errors,mesopic and photopic pupil diameters,and the mesopic and photopic kappa angles were assessed.Patients were also administered a satisfaction survey.Photic phenomena were graded by questionnaire.Independent-related factors were identified by correlation and bivariate logistic regression analyses.RESULTS： The distance from the photopic to the mesopic pupil center（pupil center shift） was significantly associated with glare/halo symptoms [odds ratio（OR）=2.065,95% confidence interval（CI）=0.916-4.679,P=0.006] and night vision problems（OR=1.832,95% CI=0.721-2.158,P=0.007）.The preoperative photopic angle kappa was significantly associated with glare/halo symptoms（OR=2.155,95% CI=1.065-4.362,P=0.041）.The photopic angle kappa was also significantly associated with glare/halo symptoms（OR=2.155,95% CI=1.065-4.362,P=0.041） and with night vision problems（OR=1.832,95% CI=0.721-2.158,P=0.007） in patients implanted with rotationally asymmetric MIOLs.CONCLUSION： A large pupil center shift and misalignment between the visual and pupillary axis（angle kappa）may play a role in the occurrence of photic phenomena after implantation of rotationally asymmetric MIOLs.

Unilateral Acute Idiopathic Maculopathy

Purpose: To discuss the fluorescein angiographic features and diagnosis as well as differential diagnosis.Methods : In our hospital, we have found three cases of UAIM, one of them has eccentric maculopathy, another has papillitis, and the third associates with pregnancy. Each has characteristic clinical findings. We have made the diagnosis base on ophthalmoscopy and fluorescein angiography (FA).Results: Three patients with UAIM have been experienced sudden unilateral decreased visual acuity. The significant changes on fundus are retinal pigment epithelium (RPE) thickening with neurosensory retinal detachment with in the macular area. FA showed early patchy hypofluorescence and hyperfluorescence at the level of the RPE.' Bull' s eye appearance may occur in the macular area after the acute stage of the disease. The clinical findings are similar to what the foreign report described. But there were no previous reports in China. Conclusion : We can establish the diagnosis on the base of clinical and fundus

Multimodal imaging in photic retinopathy

Dear Editor,We would like to present the importance of multimodal imaginginphoticretinopathyinacaseofphotic retinopathy.A young man presented with a one-day history of left central scotoma and metamorphopsia after exposure toahandheldlaserpointerbeamduringanightparty.The laser pointer was a class IIIB green laser with a wavelength of532±10nmandmaximalpower<1000mW.However.

Automated detection of myopic maculopathy from color fundus photographs using deep convolutional neural networks

Background:Myopic maculopathy(MM)has become a major cause of visual impairment and blindness worldwide,especially in East Asian countries.Deep learning approaches such as deep convolutional neural networks(DCNN)have been successfully applied to identify some common retinal diseases and show great potential for the intelligent analysis of MM.This study aimed to build a reliable approach for automated detection of MM from retinal fundus images using DCNN models.Methods:A dual-stream DCNN(DCNN-DS)model that perceives features from both original images and corresponding processed images by color histogram distribution optimization method was designed for classification of no MM,tessellated fundus(TF),and pathologic myopia(PM).A total of 36,515 gradable images from four hospitals were used for DCNN model development,and 14,986 gradable images from the other two hospitals for external testing.We also compared the performance of the DCNN-DS model and four ophthalmologists on 3000 randomly sampledfundus images.Results:The DCNN-DS model achieved sensitivities of 93.3%and 91.0%,specificities of 99.6%and 98.7%,areas under the receiver operating characteristic curves(AUCs)of 0.998 and 0.994 for detecting PM,whereas sensitivities of 98.8%and 92.8%,specificities of 95.6%and 94.1%,AUCs of 0.986 and 0.970 for detecting TF in two external testing datasets.In the sampled testing dataset,the sensitivities of four ophthalmologists ranged from 88.3%to 95.8%and 81.1%to 89.1%,and the specificities ranged from 95.9%to 99.2%and 77.8%to 97.3%for detecting PM and TF,respectively.Meanwhile,the DCNN-DS model achieved sensitivities of 90.8%and 97.9%and specificities of 99.1%and 94.0%for detecting PMand T,respectively.Conclusions:The proposed DCNN-DS approach demonstrated reliable performance with high sensitivity,specificity,and AUC to classify different MM levels on fundus photographs sourced from clinics.It can help identify MM automatically among the large myopic groups and show great potential for real-life applications.

Acute macular neuroretinopathy following COVID-19 infection:Three case reports

BACKGROUND During the Coronavirus disease 2019(COVID-19)pandemic,a notable increase in acute macular neuroretinopathy(AMN)cases was observed.This study aimed to investigate the potential association between AMN and COVID-19 by examining 3 cases in China.CASE SUMMARY The first case involved a 30-year-old man who presented with progressive vision loss following a COVID-19 infection.Optical coherence tomography(OCT)and near-infrared imaging identified hallmark AMN lesions,hyperreflective disruptions within the outer plexiform layer,and hyporeflective anomalies in the ellipsoid zone,leading to an AMN diagnosis.Despite partial visual recovery,OCT angiography(OCTA)revealed persistent microvascular changes,specifically a decreased vascular density in the deep capillary plexus.The second case was a 24-year-old woman who experienced blurred vision and exhibited bilateral cottonwool spots on fundus examination post-COVID-19.Imaging confirmed the presence of AMN along with paracentral acute middle maculopathy(PAMM).Follow-up OCTA found a progressive reduction in vascular density,indicating ongoing microvascular compromise.The third case was a 28-year-old woman who reported sensations of occlusion in her right eye following a COVID-19 infection.Imaging confirmed both AMN and PAMM,revealing similar decreases of microvascular density on OCTA despite a significant improvement in visual acuity.We noted that all 3 patients had received the COVID-19 vaccine prior to the appearance of symptoms.CONCLUSION The findings highlight the diagnostic utility of advanced ocular imaging in detecting AMN in COVID-19 patients and the importance of comprehensive eye examinations.

杞菊地黄丸联合施图伦治疗肝肾不足型近视萎缩性黄斑病变临床研究

目的观察杞菊地黄丸联合施图伦治疗肝肾不足型近视萎缩性黄斑病变(MAM)患者的临床疗效。方法选择2021年1月—2022年12月于山东中医药大学附属眼科医院眼底外科门诊就诊的60例肝肾不足型MAM患者为研究对象,采用随机数字表法分为对照组和治疗组各30例(30只眼)。对照组给予施图伦点患眼,治疗组在施图伦点眼基础上口服杞菊地黄丸,2组疗程均为30 d。比较2组患者治疗前后中医证候评分和相关眼参数(裸眼及最佳矫正视力、等效球镜度、光敏感度、视野平均缺损、黄斑中心凹视网膜厚度、黄斑中心凹下脉络膜厚度),并比较2组不同近视性黄斑病变(MMD)分级[弥漫性脉络膜视网膜萎缩(C2级)、斑片状脉络膜视网膜萎缩(C3级)、黄斑萎缩(C4级)]患者相关眼参数。结果治疗后,2组中医证候积分均较治疗前明显降低(P均<0.05),且治疗组明显低于对照组(P<0.05)。治疗后,2组裸眼及最佳矫正视力与治疗前比较及组间比较差异均无统计学意义(P均>0.05),但治疗组C2级患者裸眼及最佳矫正视力均明显高于治疗前及对照组(P均<0.05);治疗组总体光敏感度明显高于治疗前及对照组(P均<0.05),其中C2和C3级患者(其中C2级疗效最佳)光敏感度明显高于治疗前及同级对照组(P均<0.05);2组等效球镜度、黄斑中心凹视网膜厚度、黄斑中心凹下脉络膜厚度与治疗前比较及组间比较差异均无统计学意义(P均>0.05),且不同分级患者比较差异均无统计学意义(P均>0.05)。结论杞菊地黄丸联合施图伦治疗肝肾不足型MAM患者疗效确切,可有效改善患者中医证候和光敏感度,有效提高病变早期(C2级)患者的裸眼及最佳矫正视力。