Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.

Central Retinal Vein Occlusion in Healthy Young Adults Following COVID-19 Vaccination: Case Series

Our aim is to report 4 cases of central retinal vein occlusion following COVID-19 vaccine administration. In this case series, 4 patients between 23-32 years of age presented to us with unilateral central retinal vein occlusion after 2-15 days of getting vaccinated against COVID-19. One patient was a known case of hypertension and 1 was hypothyroid. All the patients had disc swelling, flame shaped haemorrhages, dilated and tortuous blood vessels in the retina. One patient had cystoid macular edema and was treated with intravitreal ranibizumab. As there were no positive systemic risk factors or incidents, COVID-19 vaccines might have an association with the central retinal vein occlusion in these cases. .

Real-World Study on the Treatment of Macular Edema in Central Retinal Vein Occlusion Using Traditional Chinese Medicine(TCM)and Its Medication Guidelines

Object:The aim is to evaluate how effective Traditional Chinese Medicine(TCM)is in treating patients who have central retinal vein occlusion with macular edema(CRVO-ME)in a real-world study.Furthermore,the objective of the research was to examine the TCM prescription trends in the management of CRVO-ME.Method:A single-center real-world study(RWS)was carried out over a span of 19 years,following the established design.The study encompassed 113 patients diagnosed with CRVO-ME.Out of these,74 patients received TCM treatment,while the remaining individuals underwent a combined therapy involving TCM and anti-VEGF drugs through intravitreal injection.The patients were matched using propensity score matching(PSM).The result measured in the RWS was BCVA.The oral prescriptions for CRVO-ME that led to observable and effective outcomes were collected.Excel and the TCM Inheritance Auxiliary Platform V2.5 were utilized to optimize mutual information,hierarchical clustering based on entropy,and other techniques to extract medication regulations and features.Result:After applying PSM,each group comprised 29 cases.Both groups exhibited improved BCVA following treatment;however,there was no statistically significant distinction in BCVA or effectiveness between the two groups(all P>0.05).Apart from the analysis of oral prescriptions for CRVO-ME,the investigation pinpointed the most frequently used TCMs,namely Flos Carthami,Semen Persicae,Radix Angelica sinensis,Radix Rehmanniae,and Radix et Rhizoma Notoginseng.Frequently utilized medications tended to possess cold,warm,or mild attributes and exhibited a taste profile that was either bitter or sweet.The primary meridians associated with the medicines employed in treating CRVO-ME were liver,spleen,stomach,heart,and lung.Through the application of association rule analysis,it was discerned that there were 195 commonly employed combinations of medicines.Additionally,a complex system entropy cluster analysis unveiled 13 key combinations of medicines.By employing an unsupervised entropy hierarchical clustering analysis,a novel prescription was formulated.Conclusion:Within a real-world population of CRVO-ME patients,TCM exhibited its effectiveness.The treatment approach for CRVO-ME predominantly involved the regulation of qi(Qi is an exceedingly subtle substance within the human body,brimming with vitality and ceaseless motion.It constitutes the fundamental element that shapes and sustains the various processes of human life.)and blood as well as the resolution of dampness.The oral prescriptions frequently targeted the meridians of liver,spleen,stomach,heart,and lungs.

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.

Comparative Quantitative Analysis of Retinal Superficial Capillary Plexus in Patients with Retinal Vein Occlusion and Unaffected Fellow Eyes

Purpose: To evaluate optical coherence tomography angiography (OCT-A) data obtained from the superficial retinal capillary plexus of patients with retinal vein occlusion and comparative analysis with data registered from unaffected fellow eyes. Methods: The examined patients were classified into 2 groups: group 1—eyes with established retinal vein occlusion (n = 29) and group 2—unaffected fellow eyes of patients with retinal vein occlusion (n = 24). The scanning protocol “Angiography 3 × 3 mm” of Zeiss Cirrus HD-OCT 6000, AngioPlex Metrix was used to evaluate the retinal superficial capillary plexus. The analyzed parameters were vascular density and perfusion density, as well as the area, perimeter, and circularity of the foveolar avascular zone (FAZ). Results: The comparative analysis of FAZ parameters at the superficial capillary plexus (SCP) between group 1 (eyes with retinal vein occlusion) and group 2 (unaffected fellow eyes) showed significant results for the three parameters, respectively area (p = 0.003), perimeter (p ≤ 0.001), and circularity (p = 0.011) of FAZ. The comparative analysis of the vascular network at SCP in patients with diagnosed retinal vein occlusion and unaffected fellow eyes showed significant results for vascular density (VD) in the central (p = 0.038) and inner (p ≤ 0.001) zones as well as total VD (p ≤ 0.001) were statistically significant. Moreover, the results obtained in the study of vascular perfusion (VP) indicated significant results in the inner zone (p ≤ 0.001) and total VP (p = 0.001). Vascular perfusion in the central zone (p = 0.116) was the only parameter not to meet significant results. Conclusion: The current study observed a significant enlargement of the FAZ and loss of its circularity, along with a reduction in vascular network parameters at the superficial retinal capillary plexus level.

Intelligent diagnosis of retinal vein occlusion based on color fundus photographs

AIM:To develop an artificial intelligence(AI)diagnosis model based on deep learning(DL)algorithm to diagnose different types of retinal vein occlusion(RVO)by recognizing color fundus photographs(CFPs).METHODS:Totally 914 CFPs of healthy people and patients with RVO were collected as experimental data sets,and used to train,verify and test the diagnostic model of RVO.All the images were divided into four categories[normal,central retinal vein occlusion(CRVO),branch retinal vein occlusion(BRVO),and macular retinal vein occlusion(MRVO)]by three fundus disease experts.Swin Transformer was used to build the RVO diagnosis model,and different types of RVO diagnosis experiments were conducted.The model’s performance was compared to that of the experts.RESULTS:The accuracy of the model in the diagnosis of normal,CRVO,BRVO,and MRVO reached 1.000,0.978,0.957,and 0.978;the specificity reached 1.000,0.986,0.982,and 0.976;the sensitivity reached 1.000,0.955,0.917,and 1.000;the F1-Sore reached 1.000,0.9550.943,and 0.887 respectively.In addition,the area under curve of normal,CRVO,BRVO,and MRVO diagnosed by the diagnostic model were 1.000,0.900,0.959 and 0.970,respectively.The diagnostic results were highly consistent with those of fundus disease experts,and the diagnostic performance was superior.CONCLUSION:The diagnostic model developed in this study can well diagnose different types of RVO,effectively relieve the work pressure of clinicians,and provide help for the follow-up clinical diagnosis and treatment of RVO patients.

Microvascular changes after conbercept therapy in central retinal vein occlusion analyzed by optical coherence tomography angiography

AIM: To investigate microvascular changes in eyes with central retinal vein occlusion(CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity(BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography(OCTA) automatic measurements of the vessel density in the superficial(SCP) and deep retinal capillary plexus(DCP), the foveal avascular zone(FAZ) area, the FAZ perimeter(PERIM), the vessel density within a 300-μm wide ring surrounding the FAZ(FD-300), the acircularity index(AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age-and sexmatched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were allsignificantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher(all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65(P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness.CONCLUSION: OCTA enables the non-invasive, layerspecific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

Intravitreal injection of bevacizumab alone or with triamcinolone acetonide for treatment of macular edema caused by central retinal vein occlusion

AIM: To compare the efficacy and safety of intravitreal bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with macular edema caused by central retinal vein occlusion (CRVO) in Chinese patients. METHODS: Seventy-five eyes of 75 patients were enrolled in this prospective, randomized, consecutive study. Thirty-six patients in group 1 were treated with an intravitreal injection of bevacizumab (1.25mg/0.05mL), and 39 patients in group 2 were treated with intravitreal bevacizumab (1.25mg/0.05mL) combined with triamcinolone acetonide (2mg/0.05mL). The main outcomes of the mean best corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) were measured. RESULTS: In group 1, the mean BCVA improved from 37.78 +/- 6.14 (baseline) to 48.06 +/- 3.86, 46.48 +/- 4.77 and 44.18 +/- 5.78 at four, six and twelve weeks post-injection, respectively (P<0.01, P=0.03, P=0.04). In group 2, the mean BCVA improved from 35.92 +/- 6.20 (baseline) to 50.69 +/- 4.22, 48.76 +/- 5.59 and 45.70 +/- 6.56 at the same time points (P<0.01 each). However, there was no significant differences in the mean BCVA (F=0.043, P=0.836) and CRT (F=0.374, P=0.544) between these two groups. During the follow-up, five patients in group 1 and six patients in group 2 with high IOP were controlled with anti-glaucoma drugs. CONCLUSION: Intravitreal injection of bevacizumab alone or combined with triamcinolone acetonide has a short beneficial effect in Chinese patients with macular edema caused by CRVO, but there is no significant difference between the two groups.

Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion

AIM：To investigate the predictive factors for shortterm effects of intravitreal bevacizumab injections on central subfield foveal thickness（CSFT）in patients with macular edema（ME）secondary to central retinal vein occlusion（CRVO）.·METHODS：This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO.Follow-up was three months.The Early Treatment Diabetic Retinopathy Study（ETDRS）score and CSFT measured by spectral-domain optical coherence tomography（SD-OCT）were used to observe the changes in best-corrected visual acuity（BCVA）.Baseline BCVA,CSFT,age,CRVO duration and the presence of cystoid macular edema（CME）or subretinal fluid（SRF）were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections.·R ESULTS：BCVA improved from 0.9 log MAR at baseline to 0.6 log MAR at 3mo,which was associated with a significant reduction in CSFT from 721μm to 392μm 3mo after injection.About 50%of CME cases and more than90%of SRF cases responded to treatment with a complete resolution at 3mo.Age（=0.036）and low baseline CSFT（=0.037）were associated with a good 3-month prognosis.Patients〉60 years old achieved better CME resolution（=0.031）and lower CSFT at 3mo（305μm 474μm,=0.003）.·CONCLUSION：Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo.Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes.The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF.

Ocular hypertension in patients with central/hemicentral retinal vein occlusions： cumulative prevalence and management

AIM： To prospectively evaluate the cumulative prevalence and the management of ocular hypertension（OH） in patients with unilateral acute central/hemicentral retinal vein occlusions（C/HCRVOs） over the course of 3 y. METHODS： The study included 57 patients with unilateral acute C/HCRVOs. All patients underwent a comprehensive ophthalmological examination of both eyes. OH associated with C/HCRVO in patients showing a score 〉5% for the risk of conversion to primary open angle glaucoma（POAG） was treated with OH medication. The treatment aimed for a decrease in intraocular pressure（IOP） to 〈21 mm Hg with a 〉22% reduction from the initial values. The cumulative prevalence of OH and the effectiveness of treatment assessed by the cumulative prevalence of conversion from OH to POAG, were estimated. RESULTS： Fifteen patients had OH associated with C/HCRVOs, the cumulative prevalence of OH was 29.4%（95% confidence interval, 16.9-41.9）. The mean value of the risk score of OH conversion to POAG for the 5 subsequent years was 11.7%±5.4%. The IOP significantly decreased from 25.67±2.16 mm Hg to 18.73±2.96 mm Hg. None of the OH patients converted to POAG during the follow-up period. CONCLUSION： The increased cumulative prevalence of OH in C/HCRVO patients indicates that OH is a risk factor for the appearance of venous occlusion. Patients with OH associated with C/HCRVO must be considered to be at high risk for conversion to POAG. Treatment with OH medications prevented conversion to POAG during the 3-year follow-up.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion

AIM:To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy(NAION)and central retinal artery occlusion(CRAO)and develop a predictive diagnostic nomogram.METHODS:The study included 37 patients with monocular NAION,20 with monocular CRAO,and 24 with hypertension.Gender,age,and systemic diseases were recorded.Blood routine,lipids,hemorheology,carotid and brachial artery doppler ultrasound,and echocardiography were collected.The optic disc area,cup area,and cup-to-disc ratio(C/D)of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured.RESULTS:The carotid artery intimal medial thickness(C-IMT)of the affected side of the CRAO group was thicker(P=0.039)and its flow-mediated dilation(FMD)was lower(P=0.049)than the NAION group.Compared with hypertension patients,NAION patients had higher whole blood reduced viscosity low-shear(WBRV-L)and erythrocyte aggregation index(EAI;P=0.045,0.037),and CRAO patients had higher index of rigidity of erythrocyte(IR)and erythrocyte deformation index(EDI;P=0.004,0.001).The optic cup and the C/D of the NAION group were smaller than the other two groups(P<0.0001).The diagnostic prediction model showed high diagnostic specificity(83.7%)and sensitivity(85.6%),which was highly related to hypertension,the C-IMT of the affected side,FMD,platelet(PLT),EAI,and C/D.CONCLUSION:CRAO patients show thicker C-IMT and worse endothelial function than NAION.NAION and CRAO may be related to abnormal hemorheology.A small cup and small C/D may be involved in NAION.The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.

Efficacy of conbercept after switching from bevacizumab/ranibizumab in eyes of macular edema secondary to central retinal vein occlusion

AIM: To explore the efficacy of conbercept after switching from bevacizumab/ranibizumab in eyes of central retinal vein occlusion(CRVO) through optical coherence tomography angiography(OCTA). METHODS: Patients with prior treatment of a minimum of three consecutive intravitreal injections of either bevacizumab or ranibizumab, followed by injection of conbercept, were recruited. The minimal follow-up period after switching was 12 mo. Central retinal thickness(CRT), best-corrected visual acuity(BCVA), the interval of injections was reviewed. Perfusion density(PD) and vascular length density(VLD) of superficial and deep capillary plexus were acquired from OCTA images before and after switching. RESULTS: Twenty-four eyes were included. CRT significantly decreased from 460.71±153.23 μm(before switching) to 283.92±38.27 μm at the end of follow-up(P<0.001). However, BCVA gained to some extent(from 0.98±0.33 to 0.76±0.42 log MAR) but the difference was not significant(P=0.070). After switching to conbercept the injection interval extended from 5.2±2.3 wk to 8.3±3.9 wk(P=0.012). At the end of follow-up, PD of deep retinal layer decreased significantly compared with before switching(from 34.62%±5.27% to 33.26%±5.82%, P=0.016), similar result was found in VLD of deep retinal layer but not in PD or VLD in superficial layer.CONCLUSION: In cases of refractory macular edema secondary to CRVO, switching to conbercept improves macular thickness and extends interval of injection. Retinal microvasculature cannot improve with treatment of conbercept.

Correlation between obstructive sleep apnea and central retinal vein occlusion

To investigate the possible correlation between obstructive sleep apnea(OSA) and central retinal vein occlusion(CRVO). Thirty consecutive patients with a recent(<3 mo)CRVO and an age-and sex-matched group of 30 control subjects were recruited. All subjects underwent full-night polysomnography to measure apnea-hypopnea index(AHI)and oxygen desaturation index(ODI). The average AHI and ODI were significantly higher in CRVO patients(AHI:13.86±8.63, ODI: 9.21±4.47) than in control subjects(AHI:8.51±6.36, ODI: 5.87±3.18;P=0.008 and 0.001 respectively).Additionally, the AHI was positively correlated with body mass index(BMI;r=0.476, P=0.017) and ODI(r=0.921,P<0.01) in both CRVO and control subjects. According to AHI scores, twenty-two(73.33%) CRVO patients had OSA and 12(40.00%) control subjects had OSA, a difference that was statistically significant(P=0.019). OSA may be a risk factor for or a trigger of CRVO development.

Altered brain network centrality in patients with retinal vein occlusion: a resting-state fMRI study

AIM:To explore the intrinsic brain activity variations in retinal vein occlusion(RVO)subjects by using the voxel-wise degree centrality(DC)technique.METHODS:Twenty-one subjects with RVO and twentyone healthy controls(HCs)were enlisted and underwent the resting-state functional magnetic resonance imaging(rs-f MRI)examination.The spontaneous cerebrum activity variations were inspected using the DC technology.The receiver operating characteristic(ROC)curve was implemented to distinguish the DC values of RVOs from HCs.The relationships between DC signal of definite regions of interest and the clinical characteristics in RVO group were evaluated by Pearson’s correlation analysis.RESULTS:RVOs showed notably higher DC signals in right superior parietal lobule,middle frontal gyrus and left precuneus,but decreased DC signals in left middle temporal gyrus and bilateral anterior cingulated(BAC)when comparing with HCs.The mean DC value of RVOs in the BAC were negatively correlated with the anxiety and depression scale.CONCLUSION:RVO is associated aberrant intrinsic brain activity patterns in several brain areas including painrelated as well as visual-related regions,which might assist to reveal the latent neural mechanisms.

Intraocular pressure modifications in patients with acute central/hemicentral retinal vein occlusions

Intraocular pressure(IOP)modifications in patients with acute central/hemicentral retinal vein occlusions(RVOs)consist in IOP reductions and increases.The IOP reduction is due to a transitional hyposecretory phase of the aqueous humor,that increases gradually until 3 mo after the venous occlusion onset,and then finally disappears after month 4 th.The IOP increases lead to the ocular hypertension and glaucoma.The possible pathogenetic correlations between ocular hypertension/glaucoma and acute central/hemicentral RVOs have been classified into three groups:1)the venous occlusion precedes the ocular hypertension/glaucoma causing neovascular glaucoma and secondary angle-closure glaucoma without rubeosis;2)the ocular hypertension and the glaucoma precede the venous occlusion and favor its appearance(ocular hypertension,primary angle-closure,primary angle-closure glaucoma,and open angle glaucomas);and 3)the venous occlusion and the ocular hypertension/glaucoma are mostly age dependent appearances due to common vascular and collagen alterations,lacking a causal connection between the 2 conditions.

Correlation between macular ganglion cell-inner plexiform layer thickness and visual acuity after resolution of the macular edema secondary to central retinal vein occlusion

AIM： To examine the thickness of the ganglion cell-inner plexiform layer（GCIPL） in eyes with resolved macular edema（ME） in non-ischemic central retinal vein occlusion（CRVO）, applying spectral-domain optical coherence tomography（SD-OCT）, and its relationship with visual acuity.METHODS： The retrospective observational case-control study included 30 eyes of non-ischemic CRVO patients with resolved ME（ME eyes） after treatment, and 30 eyes of non-ischemic CRVO patients without ME（non-ME eyes）. The macular GCIPL thickness, peripapillary retinal nerve fiber layer（p RNFL） thickness and central macular thickness（CMT） were measured on a SD-OCT scan. Linear regression analyses were performed to determine the correlation between the thickness of each and the visual acuity（VA）.RESULTS： No significant difference in average GCIPL thickness, mean pR NFL thickness and CMT were observed between ME group and non-ME group（P=0.296, 0.183, 0.846）. But, minimum GCIPL thickness was reduced in ME eyes compared with non-ME eyes（P=0.022）. Final VA significantly correlated with the minimum GCIPL thickness in ME eyes（r=-0.482, P=0.007）, whereas no correlation was found with average GCIPL thickness, average pR NFL thickness and mean CMT.CONCLUSION： Minimum GCIPL thickness is reduced in ME eyes compared with non-ME eyes, and correlated with the VA in non-ischemic CRVO. These results propose that inner retinal damage occurring in patients with ME secondary to non-ischemic CRVO may lead to permanent visual defect after treatment.

Comment on “Correlation between macular ganglion cell-inner plexiform layer thickness and visual acuity after resolution of the macular edema secondary to centralretinal vein occlusion”

Dear Editor,We would like to address several issues with the study of Kim et a". The study was retrospectively conducted with the existence of a selection bias attributable to inclusion of 2 completely different etiologic subgroups of patients with nonischemic central retinal vein occlusion (CRVO), namely, patients older than 50y, who usually have common systemic conditions such as hypertension and diabetes;and patients younger than 50y, in whom other mechanisms, such as the hyperviscosity syndrome or inflammatory condition, should be specifically considered.

Comparison of efficacy of conbercept,aflibercept,and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion:a Meta-analysis

AIM:To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor(VEGF)drugs in the treatment of macular edema(ME)due to retinal vein occlusion(RVO)based on the evidence pooled from current clinical trials and observational studies.METHODS:A systematic literature search was conducted on nine online databases from inception until April 30,2022.The main endpoints were best corrected visual acuity(BCVA),central macular thickness(CMT),and adverse events(AEs).Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs.The retrieved data were analyzed using Stata software(version 12.0).RESULTS:A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis.It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo[weight mean difference(WMD)=-0.03,P=0.001;WMD=-0.05,P=0.019],but the effects were not different from that of ranibizumab at 6mo.Moreover,there was not statistically significant dif ference in the propor tion of patients gaining≥15 letters at 12-24mo between aflibercept and ranibizumab[odds ratio(OR)=1.16,P=0.427].Conbercept had higher mean CMT change effects at 1mo(WMD=-14.43,P=0.014)and 6mo(WMD=-35.63,P≤0.001)compared with ranibizumab.Meanwhile,the mean CMT change effects at 1mo(WMD=-10.14,P=0.170),6mo(WMD=-26.98,P=0.140)and 12-24mo(WMD=-12.34,P=0.071)were comparable among the groups.Similarly,AEs were not significantly different among the treatments(OR=0.75,P=0.305;OR=1.04,P=0.89).The stability of effect size of mean BCVA and CMT improved with the increase in sample size.Aflibercept and conbercept required fewer injections compared with ranibizumab.CONCLUSION:This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept,ranibizumab,and aflibercept in the treatment of RVOME.Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab.Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion

AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:This is a retrospective case control study.The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor(VEGF)for patients diagnosed with macular edema secondary to DR(DME)or RVO(RVO-ME)at Xijing Hospital from August 2021 to July 2022.Meanwhile,aqueous humor samples during vitrectomy from patients with idiopathic macular hole(IMH)were also collected and served as controls.The aqueous humor concentrations of VEGF,platelet-derived factor(PDGF),interleukin(IL)-6,IL-8,IL-18,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured with Human Premixed Multi-Analyte Kit(Luminex).The difference of the aqueous cytokines and the correlation between the two diseases were analyzed.RESULTS:A total of 40 eyes of 38 patients were enrolled in the study,including 13 eyes of 11 DME patients(DME group),16 eyes of 16 RVO-ME patients(RVO-ME group)and 11 eyes of 11 IMH patients(control group).The VEGF,PDGF,IL-6,IL-8,and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group(all P<0.05),the levels of TNF-αwas higher in the DME group than in the control group(P<0.05).The VEGF,IL-6,MCP-1,and TNF-αlevels in the aqueous humor were significantly higher in the DR group than those in the RVO group(all P<0.05).Correlation analyses revealed that there were complex positive correlations between IL-6,IL-8,IL-18,MCP-1,and TNF-αlevels in the aqueous humor of eyes with two diseases.CONCLUSION:Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME,the roles of these factors are more significant or more likely to be activated in DR patients,suggesting different treatment strategies should be considered for the two diseases.

Optical coherence tomography angiography for macular microvessels in ischemic branch retinal vein occlusion treated with conbercept:predictive factors for the prognosis

AIM:To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography(OCTA)in ischemic branch retinal vein occlusion(BRVO)patients with macular edema(ME)after anti-vascular endothelial growth factor(VEGF)treatment.METHODS:In this retrospective analysis,data from 60 patients(60 eyes)with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography(FFA)were studied.The eyes with ME according to spectral domain optical coherence tomography(SD-OCT)underwent intravitreal conbercept(IVC)and 3+pro re nata(PRN)regimen.The injection times were recorded.Two weeks after injection,fundus laser photocoagulation was performed in the non-perfusion area of the retina.The patients were followed up once a month for 6mo.The bestcorrected visual acuity(BCVA),foveal avascular zone(FAZ),and A-circularity index(AI),at 6mo and the baseline were compared.RESULTS:All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR(P<0.001).The mean central macular thickness(CMT)significantly decreased from 476.22±163.54 to 298.66±109.23μm.Both the FAZ area and AI at 6mo were significantly higher than those at the baseline:the FAZ area increased(0.38±0.02 vs 0.39±0.02 mm^(2),P<0.05);the AI increased(1.27±0.02 vs 1.31±0.01,P=0.000).The baseline BCVA showed a significantly positive correlation with the baseline FAZ area,FAZ perimeter(PERIM)and AI,final visual gain(FVG)and injection times,respectively(P<0.001).FVG showed a significantly negative correlation with the FAZ area,PERIM,AI and injection times,but a significantly positive correlation with vessel densities(VDs)300μm area around FAZ(FD-300;P<0.001).Injection times was positively correlated with the baseline FAZ area,and AI,but inversely correlated with the baseline FD-300(P<0.001).However macular ischemia was noted in 5 cases during follow-up.CONCLUSION:Using OCTA to observe macular ischemia and quantify parameters can better predict the final visual prognosis of patients before treatment.The changes in FAZ parameters may influence the visual prognosis and injection times.