Unified deep learning model for predicting fundus fluorescein angiography image from fundus structure image

The prediction of fundus fluorescein angiography(FFA)images from fundus structural images is a cutting-edge research topic in ophthalmological image processing.Prediction comprises estimating FFA from fundus camera imaging,single-phase FFA from scanning laser ophthalmoscopy(SLO),and three-phase FFA also from SLO.Although many deep learning models are available,a single model can only perform one or two of these prediction tasks.To accomplish three prediction tasks using a unified method,we propose a unified deep learning model for predicting FFA images from fundus structure images using a supervised generative adversarial network.The three prediction tasks are processed as follows:data preparation,network training under FFA supervision,and FFA image prediction from fundus structure images on a test set.By comparing the FFA images predicted by our model,pix2pix,and CycleGAN,we demonstrate the remarkable progress achieved by our proposal.The high performance of our model is validated in terms of the peak signal-to-noise ratio,structural similarity index,and mean squared error.

Application of non-mydriatic fundus photography-assisted telemedicine in diabetic retinopathy screening

BACKGROUND Early screening and accurate staging of diabetic retinopathy(DR)can reduce blindness risk in type 2 diabetes patients.DR’s complex pathogenesis involves many factors,making ophthalmologist screening alone insufficient for prevention and treatment.Often,endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early intervention.AIM To explore the efficacy of non-mydriatic fundus photography(NMFP)-enhanced telemedicine in assessing DR and its various stages.METHODS This retrospective study incorporated findings from an analysis of 93 diabetic patients,examining both NMFP-assisted telemedicine and fundus fluorescein angiography(FFA).It focused on assessing the concordance in DR detection between these two methodologies.Additionally,receiver operating characteristic(ROC)curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine,using FFA outcomes as the standard benchmark.RESULTS In the context of DR diagnosis and staging,the kappa coefficients for NMFPassisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively,indicating substantial intermethod agreement.Moreover,the NMFP-assisted telemedicine’s predictive accuracy for positive FFA outcomes,as denoted by the area under the ROC curve,was remarkably high at 0.955,within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than 0.001.This predictive model exhibited a specificity of 100%,a sensitivity of 90.9%,and a Youden index of 0.909.CONCLUSION NMFP-assisted telemedicine represents a pragmatic,objective,and precise modality for fundus examination,particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic patients.Its implementation in these scenarios is of paramount significance,enhancing the clinical accuracy in the diagnosis and therapeutic management of DR.This methodology not only streamlines patient evaluation but also contributes substantially to the optimization of clinical outcomes in DR management.

Fundus photography,fundus fluorescein angiography,and optical coherence tomography of healthy cynomolgus monkey,New Zealand rabbit,Sprague Dawley rat,and BALB/c mouse retinas

Background:A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis.The choice of animal model is based on the measurability of specific parameters or structures,the applicability of clinical measurement technologies,and the similarity to human eye function.Studies of eye pathology usually compare optical parameters between a healthy and altered state,so accurate baseline assessments are critical,but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.Methods:Three cynomolgus monkeys,six New Zealand rabbits,ten Sprague Dawley(SD)rats,and BALB/c mice were examined by fundus photography(FP),fundus fluorescein angiography(FFA),and optical coherence tomography(OCT).Results:Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP,FFA,and OCT.New Zealand rabbits have large eyeballs,but they have large optic disc and myelinated retinal nerve fibers in their retinas,and the growth pattern of retinal vessels were also different to the human retinas.Unlike monkeys and rabbits,the retinal vessels of SD rats and BALB/c mice were widely distributed and clear.The OCT performance of them were similar with human beings except the macular.Conclusions:Monkey is a good model to study changes in retinal structure associated with fundus disease,rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases,and rats and mice are good models for retinal vascular diseases.These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.

Comparison of fundus fluorescein angiography and fundus photography grading criteria for early diabetic retinopathy

AIM:To compare the assessment outcomes of the characteristics of mild to moderate non-proliferative diabetic retinopathy(NPDR) established by fundus photography and fundus fluorescein angiography(FFA).METHODS:The fundus photos and FFA results of 260 patients with diabetes mellitus were reviewed.Diabetic retinopathy(DR) severity was graded based on the international classification standard.The microaneurysms,hemorrhages,and intraretinal microvascular abnormalities(IRMA) in FFA images of patients with mild to moderate NPDR were observed.The differences between the fundus photos and the FFA results were summarized,analyzed,and compared.RESULTS:The counting of intraretinal hemorrhages identified by FFA revealed that only 9 eyes(1.9%) had more than 20 intraretinal hemorrhages in all four quadrants;15 eyes(3.1%) had more than 20 intraretinal hemorrhages in three quadrants;26 eyes(5.4%) had over 20 intraretinal hemorrhages in two quadrants;and 37 eyes(7.7%) had more than 20 intraretinal hemorrhages in only one quadrant.Furthermore,the number of IRMAs appeared ≥4 in 17 eyes,3 in 35 eyes,2 in 69 eyes,and 1 in 93 eyes.CONCLUSION:FFA has higher detection accuracy of retinal angiopathy than fundus photography.FFA grading results are helpful for timely detection and proper treatment of lesions easily missed by fundus photography.

Can Fundus Fluorescein Angiography be Performed for Diabetic Patients on Oral Metformin

Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography （FFA） remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy（CIN） and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.

OCTA characteristics in non-arteritic central retinal artery occlusion and correlation with visual acuity

AIM:To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion(NA-CRAO)via optical coherence tomography angiography(OCTA)and analyze their correlation with visual acuity.METHODS:Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into:A type(mild n=29),B type(moderate n=27)and C type(severe n=6)based on the degree of visual loss,retinal edema,and arterial blood flow delay in fundus fluorescence angiography(FFA).Contralateral healthy eyes were used as the control group.Best-corrected visual acuity(BCVA),slit lamp microscopy,indirect ophthalmoscopy,fundus color photography,OCTA,and FFA were performed.Spearman’s correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity.RESULTS:There were no statistically significant differences in age,gender,and intraocular pressure among the three types and the control group(P>0.05).Vessel density in deep capillary plexus(VD-DCP)significantly decreased(P<0.05)in all three types of NA-CRAO patients compared to the control group.Vessel density in superficial vascular plexus(VD-SVP)significantly decreased(P<0.05)in type A patients and choriocapillaris flow area significantly decreased(P<0.05)in type B and type C patients compared to the control group;while outer retinal flow areas significantly increased in the type A(P<0.05)and decreased in type C patients(P<0.05).The retinal thickness significantly increased in type C group(P<0.05).The VD-SVP at fovea in the type A was significantly lower than both of type B and C.The VD-SVP at nasal parafovea in type A and B was significantly lower than type C(P<0.05).The logMAR BCVA of type A was significantly better than that of type B and C groups(P<0.05).Spearman’s correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea(r=0.679,P=0.031)and nasal parafovea(r=0.826,P=0.013).CONCLUSION:OCTA is valuable for assessing retinal ischemia,and evaluating visual impairment.Deep retinal vasculature is commonly affected in all NA-CRAO types.VDSVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant

AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021.The clinical features,therapeutic strategies,and prognoses of all patients were reviewed.RESULTS:Five patients with a mean age of 52.00±7.23y were diagnosed as RAA.These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant.Vitreous opacity was found in all 10 eyes,and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis.The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes(29%),neovascular glaucoma in 2 eyes(29%),and iris neovascularization in 1 eye(14%).Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography(FFA)in this group of cases,and the incidence of the retinal non-perfusion area was 67%.Although no cases of retinal neovascularization were found,the prognosis of visual acuity was not ideal.CONCLUSION:This is the first report of RAA in patients with the TTR Gly83Arg variant.Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients.Thereafter,regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential.And FFA after vitrectomy is very important,which can help ophthalmologists detect RAA earlier and treat it in time.

Combined hamartoma of the retina and retinal pigment epithelium:A case report

BACKGROUND Combined hamartoma of the retina and retinal pigment epithelium(CHRRPE)is a rare congenital benign tumor which is commonly monocular.Typical CHRRPE comprises slightly raised lesions at the posterior pole,with proliferation membrane often leading to vascular distortion.In severe cases,macular edema,macular hole,retinal detachment or vitreous hemorrhage may occur.Patients with atypical clinical manifestations are prone to misdiagnosis by inexperienced ophthalmologists.CASE SUMMARY A 33-year-old man reported onset of right eye blurred vision for one week prior.Anterior segment and intraocular pressure were normal in both eyes.Left eye fundus photography was normal.Right eye ophthalmoscopy showed vitreous hemorrhage and off-white raised retinal lesions below the optic disc.Proliferative membranes on the lesion surfaces resulted in superficial retinal detachment and tortuosity and occlusion of peripheral blood vessels.A horseshoe-like tear in the temporal periphery was surrounded by retinal detachment.Optical coherence tomography revealed retinal thickening at the focal site with structural disturbance indicated by high reflectance.Right eye ultrasound showed retinal thickening at the lesion,stretching and uplifting of the proliferative membrane,with moderately patchy echo at the optic disc edge.Cytokines and antibodies were detected in vitreous fluids during the operation to rule out other diseases.Fundus fluorescein angiography(FFA)at postoperative follow-up led to final diagnosis of CHRRPE.CONCLUSION FFA is helpful in diagnosing retinal and retinal pigment epithelial combined hamartoma.In addition,other cytokine and etiological tests facilitate further differential diagnosis to rule out other suspected diseases.

Non-arteritic anterior ischemic optic neuropathy combined with branch retinal vein obstruction:A case report

BACKGROUND Non-arteritic anterior ischemic optic neuropathy(NAION)is an independent disease characterized by edematous optic discs.In eyes with branch retinal vein occlusion(BRVO),the arteries and veins in the ethmoid plate of the optic disc are relatively crowded;however,a combination of the two is clinically uncommon.Herein,we reported a patient with NAION and concealed BRVO,for which the treatment and prognosis were not similar to those for NAION alone.CASE SUMMARY Herein,we report a case of NAION with concealed BRVO that did not improve with oral medication.A week later,we switched to intravenous drug administration to improve circulation,and the patient’s visual acuity and visual field recovered.Hormonal therapy was not administered throughout the study.This case suggested that:(1)Fundus fluorescein angiography(FFA)can help detect hidden BRVO along with the NAION diagnosis;(2)intravenous infusion of drugs to improve circulation has positive effects in treating such patients;and(3)NAION with concealed BRVO may not require systemic hormonal therapy,in contrast with the known treatment for simple NAION.CONCLUSION NAION may be associated with hidden BRVO,which can only be observed on FFA;intravenous therapy has proven effectiveness.

Efficacy and safety of ranibizumab for wet age-related macular degeneration in Chinese patients

AIM： To evaluate the clinical efficacy and safety of ranibizumab for wet age-related macular degeneration （wAMD） in Chinese patients and to determine the mean number of injections administered over one year of follow-up. METHODS： This single centre, retrospective observational case series study included data from 121 patients with wAMD （121 eyes） who were diagnosed by indirect ophthalmoscopy, fluorescence fundus angiography （FFA）, indocyanine green angiography, and optical coherence tomography. Ranibizumab was injected into the vitreous cavities once per month for 3mo and as needed afterwards. Changes in visual acuity and central foveal thickness （CFT） during the follow-up period were compared, and the mean number of injections over the year was calculated. Patients with one or more adverse events related to the drugs and injections were recorded for further adverse events analysis.RESULTS： The study population included 70 males and 51 females aged between 50 and 87y （mean： 71.32±9.41y）. The mean number of injections over the first year was 5±1 （range： 3-9）. The mean best-corrected visual acuity by Early Treatment Diabetic Retinopathy Study increased from 43.2±19.3 （95%CI： 39.8-46.7） at baseline to 51.7±20.1 （95%CI： 48.1-55.3）, and central foveal thickness （CFT） decreased from 526.5±277.0 μm （95%CI： 476.6-576.4） to 258.2±161.6 μm （95%CI： 229.2-287.3） at 12mo. The differences were statistically significant （P〈0.001）. Visual acuity significantly improved in 34.1% of the patients （38 eyes）, stabilized in 66.1% of the patients （80 eyes）, and significantly decreased in 2.5% of the patients （3 eyes）. CFT at baseline was an independent risk factor of decreased CFT and increased visual acuity. None of the patients had severe adverse events during the follow-up period.CONCLUSION： Ranibizumab can effectively control disease progression and improve visual acuity in patients with wAMD. The disease conditions of most patients stabilized after a one-year treatment with an average of 5 injections.

Unilateral focal lesions in the macula as an early presentation of syphilis

A 55-year-old male complained of right eye blurry vision for 3 days. His best-corrected visual acuity(BCVA) was 0.2 for the right eye and 1.0 for the left eye. Anterior segment and vitreous body examinations of both eyes were normal. Yellowish-white focal lesions in the macula of the right eye were observed and subtly changes of lesions were found along the superotemporal and inferotemporal arcades in the macula two days later. Fluorescein fundus angiography(FFA) revealed slight fluorescent leakage from the lesions in the macula of the right eye, and segmental venous leakage and optic disc hyperfluorescence were observed in both eyes. Indocyanine green angiography(ICGA) demonstrated that the lesions in the macula of the right eye had hypofluorescence at a late stage and spectral domain optical coherence tomography(SD-OCT) imaging of the macula showed focal impairment of the inner segment and outer segment(IS/OS). The blood investigation indicated a positive treponema pallidum hemagglutination assay(TPPA) and a rapid plasma reagin test(RPR) of 1:32. After antisyphilitica treatment for 6 weeks, the yellowish-white lesions had vanished and the BCVA was 1.2 followed by restoration of the IS/OS for the right eye, with an RPR of 1:4. In conclusion, ophthalmologists should alert unilateral focal lesions in the macula may be the first sign of syphilis. Prompt treatment is highly effective in resolving vision.

Protective effects of umbilical cord mesenchymal stem cell exosomes in a diabetic rat model through live retinal imaging

AIM:To assess the protective effect of human umbilical cord mesenchymal stem cell exosomes(hucMSC-Exs)in a diabetic rat model by using a variety of retinal bioassays.METHODS:hucMSCs were subjected to differential ultracentrifugation for the collection of exosomes,and transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA)using a NanoSight analysis system and Western blotting(WB)were used to analyze the expression of surface marker proteins such as CD63,CD9 and Calnexin.Streptozotocin(STZ)was injected into the intraperitoneal cavity to establish a diabetic model.Rats were divided into a normal group,diabetic group and hucMSC-Ex group.Fundus fluorescein angiography(FFA),optical coherence tomography(OCT)and other live imaging methods were used to observe the fundus of the rats.Finally,the eyeballs of rats from each group were collected for hematoxylin-eosin(HE)staining to further analyze the retinal structure.RESULTS:Through TEM,NTA and WB,we successfully isolated hucMSC-Exs.Subsequent FFA and OCT confirmed that hucMSC-Exs effectively prevented early retinal vascular damage and thickening of the retina.Finally,HE staining of rat retinal sections revealed that exosomes effectively alleviated retinal structure disruption caused by diabetes.CONCLUSION:hucMSC-Exs have a protective effect on the retina in diabetic rat through FFA,OCT and HE staining.

The Clinical Characteristics and Imaging Findings of Morning Glory Syndrome

To investigate the features of CT, ultrasonography and fundus fluorescein angiography （FFA） of morning glory syndrome, the data on CT, A/B-scan ultrasonography and fundus fluorescein angiography （FFA） were retrospectively analyzed in 8 cases of morning glory syndrome （MGS）. Among those cases, 6 were examined with CT, 4 with FFA and 8 with A/B-scan ultrasonography. Results showed that the characteristics of CT, A/B-scan ultrasonography and FFA in MGS included： （1） The attachment spot of optic nerve became thin and vitreous body protruded to the posterior wall of eyeball with a spherical shape on CT image; （2） in the early period of FFA, hypofluorescence appeared on the optic, the abnormal arteriae and veins around the optic papilla were displayed clearly and in the late period, optic disc was stained with fluorescein; （3） on B-scan ultrasonogram, the vitreous cavity extended to the posterior pole and optic papilla, and projected to the basal part of muscle cones and thus the posterior part of vitreous cavity looked like an upside-down bottleneck. Sometimes the echogenic band of retinal detachment could also be seen. On A-scan ultrasonogram, both vitreous cavity and bottleneck showed no ultrasonic echoes and presented a base line without any evident wave crest. It is concluded that CT, A /B-scan ultrasonography and FFA could show the imageological features of MGS from different aspects, which helps clinicians to differentiate it from other diseases such as optic disc coloboma. CT and A /B-scan ultrasonography, in particular, are considered to be reliable imageological methods for the accurate diagnosis of MGS and are superior to the traditional techniques.

Multimodal imaging study of lipemia retinalis with diabetic retinopathy:A case report

BACKGROUND Lipemia retinalis(LR)is a rare disease related to hypertriglyceridemia.However,the symptoms of hypertriglyceridemia are insidious and difficult to detect without blood tests.The fundus is the only site where blood vessels can be observed directly.Understanding the specific performance of LR in multimodal imaging fundus examinations can help diagnose more patients with abnormal hyperlipidemia.CASE SUMMARY A 29-year-old woman with type 2 diabetes presented to our clinic complaining of a six-day loss of visual acuity in the left eye.The fundus color images showed typical LR:Arteries and veins were the same pink-white color.Infrared images showed hyperinfrared reflections of the arteries and veins.Optical coherence tomography(OCT)showed numerous high point-like reflections in the retinal section,corresponding to different calibers of blood vessel sections.Medium reflections were seen in the big vessels of the choroid.Fundus fluorescein angiography(FFA)and optical coherence tomography angiography(OCTA)showed no significant changes.Laboratory examination found a total cholesterol level of 13.98 mmol/L,triglyceride 20.55 mmol/L,which confirmed the diagnosis of LR.After treatment to lower blood lipids and control blood glucose,the fundus imaging showed that the blood lipids in the patient had returned to normal.CONCLUSION LR shows specific changes in fundus color photography,infrared photography,and OCT.FFA and OCTA were not sensitive to LR changes.

The Natural History of Dry Type of Age-related Macular Degeneration

To study the natural history of dry type of age-related macular degeneration (AMD) and search for a sensitive method for detecting the development of the disease, the fundus fluorescein angiography, visual acuity, electroretinogram and FM 100-hue test were used to examine 75 eyes, 147 eyes, 73 eyes, and 94 eyes respectively. These examinations were taken at least twice during the follow-up periods. The average age was 63.2 years (50-80 years ). The average follow-up was 29.8 months with a range of 3-74 ...

Characteristics of fundus autofluorescence in cystoid macular edema

Background Fundus autofluorescence （FAF） imaging is a fast and noninvasive technique developed over the last decade.The authors utilized fluorescent properties of lipofuscin to study the health and viability of the retinal pigment epithelium （RPE）-photoreceptor complex.Observing the intensity and distribution of FAF of various retinal diseases is helpful for ascertaining diagnosis and evaluating prognosis.In this study,we described the FAF characteristics of cystoid macular edema （CME）.Methods Sixty-two patients （70 eyes） with CME were subjected to FAF and fundus fluorescein angiography （FFA） by a confocal scanning laser ophthalmoscope （Heidelberg Retina Angiograph 2 （HRA2））.Characteristics of FAF images were compared with FFA images.Results FAF intensity in normal subjects was highest at the posterior pole and dipped at the fovea.All cases of CME showed fluorescein dye accumulated into honeycomb-like spaces in macular and formated a typical petaloid pattern or atypical petaloid pattern in the late phases of the angiography.Sixty-one eyes with CME on FAF images showed mild or moderate hyperautofluorescence petaloid pattern in fovea,the FAF patterns of these CME was perfectly corresponding with shape in their FFA images;nine eyes with CME secondary to exudative age related macular degeneration （AMD） showed expansion of the hypoautofluorescence without petaloid pattern in macula.Conclusion FAF imaging can be used as a new rapid,non-invasive and ancillary technique in the diagnosis of the majority of CME,except for AMD and small part of other fundus diseases.

Effect of Qiming Granule(芪明颗粒) on Retinal Blood Circulation of Diabetic Retinopathy:A Multicenter Clinical Trial

Objective： To objectively assess the effect of Qiming Granule （芪明颗粒） in the treatment of diabetic retinopathy （DR） by fluorescence fundus angiography （FFA）. Methods： In a multi-center, randomized, parallel controlled clinical trial, patients with DR were randomly assigned to the control group （calcium dobesilate capsule） and the test group （Qiming Granule）. Changes in the retinal blood circulation time were recorded by FFA after 3 months of medication. Results： Significant reduction was observed in the retinal arterio-venous circulation time （AVCT） in both groups （P〈0.01）, the value was 7.635 ± 3.149 s before treatment and 5.165 ±3.382 s after treatment in the treated group, and 7.737±3.413 s and 5.313±3.472 s in the control group respectively. Qiming Granule also reduced the arm-to-retinal circulation time （ARCT, P〈0.05）. The value was 17.867± 3.872 s before treatment and 15.643 ± 4.648 s after treatment in the treated group, and 17.217 ± 3.833 s and 16.312± 3.613 s in the control group （P〉0.05） respectively. The ARCT in the tested group was reduced, with a statistically significant difference post-medication （P〈0.01）. Conclusion： As a Chinese medicine complex prescription, Qiming Granule may alleviate retinal hypoxia and ischemia by increasing retinal blood flow and improving the blood circulation.