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.

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.

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.

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.

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.

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.

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. .

Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C

An estimated 300 million people worldwide suffer from chronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylated-interferon （pegIFN） and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C （genotype 2b）. Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-α 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.

Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C

We report a panel of severe inflammatory and vascular intraocular disorders occurring during interferon-alpha （IFN-α） treatment in eight hepatitis C virus （HCV）- infected patients. These events include three cases of Vogt-Koyanagi-Harada like （VKH） disease （an association of panuveitis, retinal detachment, ear and meningeal detachment and skin and hair changes）, two cases of central retinal vein occlusion, one case of central retinal artery occlusion, one case of severe hypertensive retinopathy and one case of bilateral ischemic optic neuropathy with severe visual impairment. Rare as they are, such severe ophthalmological complications require a close follow-up of HCV-infected patients under IFN-α breabnent with ophthalmological monitoring if any ocular manifestation occurs.

Short-term effects of intravitreal triamcinolone acetonide injection on ocular blood flow evaluated with color Doppler ultrasonography

AIM:To evaluate the changes in ocular blood flow with color Doppler ultrasonography(CDU) after intravitreal triamcinolone acetonide(IVTA) injection.METHODS:A total of 46 patients who underwent IVTA(4 mg/0.1 mL) injection for diabetic macular edema(DME)(n =22), central retinal vein occlusion(CRVO)(n =12) and choroidal neovascular membrane(CNVM)(n =12) were included in the study. Peak systolic velocity(PSV), end diastolic velocity(EDV) and resistivity index(RI) were measured from the ophthalmic artery(OA), the central retinal artery(CRA) and the posterior ciliary artery(PCA)of each patient with CDU before, at the end of the first week and at the end of the first month following IVTA injection.RESULTS:In the DME group, PSV of OA at the first of the first month(mean ±SD)(37.48 ±10.87 cm/s) increased compared to pre-injection value(31.39 ±10.84 cm/s)(P =0.048). There was a statistically significant decrease(P =0.049) in PSV of CRA at the end of the first month(7.97±2.67 cm/s) compared to the pre-injection(9.47±3.37 cm/s).There was not any statistically significant difference onthe other parameters in the DME group. Also, there was not any statistically significant difference on the ocular blood flow values in the CRVO and CNVM groups.CONCLUSION:We observed that 4 mg/0.1 mL IVTA increased PSV of OA and decreased PSV of CRA in DME patients and did not have any effect on ocular blood flow values of CRVO and CNVM patients.

Vitreous hemorrhage and fibrovascular proliferation after laser-induced chorioretinal venous anastomosis

·AIM:To describe a case in which vitrectomy was required for vitreous hemorrhage and fibrovascular proliferation after laser-induced chorioretinal venous anastomosis (LCVA) for non-ischemic central retinal vein occlusion (CRVO).·METHODS:Observational case report.·RESULTS:A 72-year-old man complained of central scotoma in the left eye,and was diagnosed as suffering from non-ischemic CRVO.LCVA was performed in another hospital.Although favorable visual function was briefly maintained postoperatively,severe vitreous hemorrhage developed in his left eye,necessitating vitrectomy.·CONCLUSION:Considering that LCVA carries a risk of serious complications,we must apply this treatment with caution,especially in ethnic groups,such as the Japanese,in whom pigmentation reacts to photocoagulation excessively.·

Endovascular recanalization of superior vena cava, brachiocephalic, and subclavian venous occlusions caused by nonmalignant lesions

Background Endovascular recanalization （EVR） is becoming the primary therapy for patients with central venous （brachiocephalic, subclavian, and superior vena cava） occlusion （CVO） caused by benign etiology. In this study, we retrospectively analyzed our experience in using EVR to treat benign CVO in 10 patients between April 2005 and September 2010. Methods The mean age of the patients was 65.3 years, 2/10 cases were female, and the origin of cause of CVO in 7/10 cases was the hemodialysis access in the upper extremity. The patients were treated with primary stent placement and evaluated with immediate technical success rate and post-interventional patency rate after the procedure. Results Eight patients were treated successfully with stent placement and experienced symptomatic relief immediately. No technical complications were observed during EVR treatment. Patients were followed up by ultrasonography and venography. Median follow-up was 13 months. Three patients required secondary procedures to maintain patency. Conclusions EVR is an effective and safe treatment in patients with benign CVO. It provides immediate symptom relief and maintains a continuous access for hemodialysis.