Adalimumab combined with Dexamethasone intravitreal implant in the treatment of refractory noninfectious uveitis macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of adalimumab combined with dexamethasone intravitreal implant in the treatment of refractory non-infectious uveitis macular edema(UME).METHODS: A total of 92 cases(131 eyes)of refractory non-infectious UME patients admitted to our hospital from January 2020 to January 2022 were selected and randomly divided into control group, with 46 cases(63 eyes)treated with dexamethasone intravitreal implant and observation group, with 46 cases(68 eyes)treated with adalimumab subcutaneous injection combined with dexamethasone intravitreal implant. The best corrected visual acuity(BCVA), central retinal thickness(CRT), vitreous opacity and Th17/Treg cytokines were measured before and after treatment, and the occurrence of adverse reactions was recorded.RESULTS: Totally 3 cases(4 eyes)were lost to follow-up. After treatment for 1, 3, 6 and 12 mo, BCVA was improved in both groups compared with that before treatment, and CRT, vitreous opacity score, serum interleukin(IL)-17 and IL-22 levels were decreased compared with those before treatment, and serum transforming growth factor-β(TGF-β)and IL-10 levels were increased compared with those before treatment. BCVA in the observation group was better than that in the control group, and CRT, vitreous opacity score, serum IL-17 and IL-22 levels were lower than those in the control group, and serum TGF-β and IL-10 levels were higher than those in the control group(all P<0.05). During treatment and follow-up, no serious adverse reactions occurred in both groups.CONCLUSION: Adalimumab combined with dexamethasone intravitreal implants in the treatment of refractory non-infectious UME can significantly subside the macular edema, reduce vitreous opacity and improve visual acuity.

Research progress on the combination therapy of diabetic macular edema / 中华眼底病杂志

Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.

Efficacy of Dexamethasone intravitreal implant combined with anti-VEGF drug in the treatment of retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy and safety of dexamethasone intravitreal implant combined with anti-VEGF drug and anti-VEGF drug monotherapy in the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A total of 133 patients(133 eyes)diagnosed with central retinal vein occlusion(CRVO)or branch vein occlusion(BRVO)secondary to macular edema in the Xiamen Eye Center of Xiamen University from June 2019 to December 2020, including 48 patients with CRVO-ME and 85 patients with BRVO-ME were analyzed. All patients were randomly assigned to monotherapy or combination therapy. The monotherapy group(66 eyes)received a monthly injection of conbercept for consecutive 3mo, followed by monthly follow-up visits; The combination therapy group(67 eyes)received once intravitreal dexamethasone implantation, and conbercept was injected once 1wk later, followed by monthly follow-up visits.All patients in the two treatment groups were evaluated at baseline and every subsequent visit until 6mo after treatment with the best corrected visual acuity(BCVA), macular central retinal thickness(CRT), and injection times of conbercept and ocular and systemic adverse events associated with intravitreal injection therapy were recorded.RESULTS: At 1, 2, 3 and 6mo after treatment, the BCVA and CRT in both groups were significantly improved than before.But there was no significant difference in the improvement of BCVA and CRT(P >0.05). From the initial intravitreal injection to 6mo, the injection times of the monotherapy group and the combination therapy group were 3.56±0.12 and 2.96±0.17 times, respectively. The injection times of the combination therapy group were significantly lower than those of the monotherapy group(P=0.004). Both the incidences of intraocular hypertension and cataract in the combination therapy group were higher than those in the anti-VEGF monotherapy group.CONCLUSION: dexamethasone intravitreal implant combined with anti-VEGF drugs is an effective method for the treatment of RVO-ME, with significantly improved visual acuity and significantly lower CRT; The combined treatment regimen can reduce the times of injections and achieve similar results to anti-VEGF drug monotherapy. However, monitoring of intraocular pressure and cataract progression is required.

Efficacy of Dexamethasone intravitreal implant in treating non-arteritic anterior ischemic optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the therapeutic effects and safety of dexamethasone intravitreal implant(DEX)on non-arteritic anterior ischemic optic neuropathy(NAION), and responses to the different course of disease.<p>METHODS: Totally 70 patients(70 eyes)in the First Affiliated Hospital of Zhengzhou University diagnosed with NAION from January 2018 to December 2020 were obtained retrospectively as combination treatment group and routine treatment group. 35 patients(35 eyes)in each group received usual care(methylprednisolne pluse therapy, microcirculation improvement and neurotrophic treatment), and combination treatment group also received a dexamethasone intravitreal implant. The best corrected visual acuity(BCVA), mean damage(MD)and pattern standard deviation(PSD)of the visual field, mean thickness of the retinal nerve fiber layer(RNFL)and intraocular pressure(IOP)were compared between the two groups, and two groups with a different course of disease before and 3mo after treatment.<p>RESULTS: BCVA and MD improved in both groups at 3mo after treatment(<i>P</i><0.05). The PSD in the combination treatment group was not significantly different before and after treatment(<i>P</i>>0.05). The PSD at 3mo after treatment in the routine treatment group was worse than before treatment(<i>P</i><0.05). BCVA, MD, and PSD in the combination treatment group had better improvement than in the routine treatment group at 3mo after treatment(<i>P</i><0.05). Visual acuity improvement rate in the combination treatment group was higher than in the routine treatment group at 3mo after treatment(<i>P</i><0.05). There was no obvious difference in RNFL thickness between the two groups(<i>P</i>>0.05). BCVA, PSD and effective rate in the combination treatment group had better improvement than in the routine treatment group in disease course ≤ 15d at 3mo after treatment(<i>P</i><0.05), and no apparent difference in the group of disease course > 15d(<i>P</i>>0.05). There was a mild and controllable increase in IOP in the combination treatment group compared to routine treatment group.<p>CONCLUSION: Dexamethasone intravitreal implant can promote BCVA and the recovery of visual function for the long term. It is deemed safe and effective in treating NAION, with better therapeutic effects within 2wk after onset.

Efficacy and safty of Dexamethasone intravitreal implant in noninfectious refractory uveitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To evaluate the efficacy and safety of dexamethasone intravitreal implant for the treatment of noninfectious refractory uveitis and analyze its influence on application and dose of systemic corticosteroids and immunosuppressive agent.<p>METHODS: This was a retrospective, case series study conducted between January 2018 and September 2019, the patients with noninfectious refractory uveitis and treated with intravitreal implantation of dexamethasone intravitreal implant were included. The best corrected visual acuity(BCVA), central retinal thickness(CRT), vitreous haze score, and intraocular pressure(IOP)at 1mo, 2mo, 4mo and 6mo after the implantation of dexamethasone intravitreal implant were compared with the baseline. Meanwhile, the dosage of corticosteroids and immunosuppressive agent used before and after the implantation of dexamethasone was also evaluated. The data was displayed as mean±standard deviation and analyzed using the paired <i>t</i>-test.<p>RESULTS: A total of 19 patients(21 eyes)were included in the present study. The mean baseline BCVA of the included patients was 0.671±0.469, while the mean CRT was 369.667±177.100μm, and the mean intraocular pressure(IOP)was 14.252±3.181mmHg. One month, 2mo, 4mo and 6mo after the injection of Ozrudex, BCVA was significantly improved compared with the baseline(<i>P</i><0.05), while the CRT and vitreous haze score were significantly reduced(<i>P</i><0.05,<i> P</i><0.05). During the follow-up period, IOP of several patients significantly increased, but normal IOP can be observed at the end of the follow-up for all included patients. At baseline, 6 patients(6 eyes)were treated with systemic corticosteroids with an average dosage of 35.8mg/d, while only 2 patients were treated with systemic corticosteroids at the end of the 6mo follow-up(5mg/d). Apart from 3 eyes with Behcet's disease which showed recurrence of macular edema between 4-6mo, no other patient underwent that. <p>CONCLUSION: Dexamethasone intravitreal implantis considered to be a safe and effective approach for non-infectious refractory uveitis which can reduce systemic medication, with significant improvement of BCVA, reduction of CRT, vitreous haze score and the dosage of systemic corticosteroids.

Efficacy and visual related quality of life of Ozurdex in the treatment of RVO-ME / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the clinical efficacy, complications and visual related quality of life(VRQoL)of Ozurdex in the treatment of macular edema secondary to retinal vein occlusion(RVO-ME). <p>METHODS: Totally 30 patients with ME, which had developed secondary to either CRVO(13 eyes)or BRVO(17 eyes), were monitored for 6mo after treatment with Ozurdex in the Department of Ophthalmology of our Hospital. We measured the best corrected visual acuity(BCVA), intraocular pressure(IOP), central macular thickness(CMT)at different time after treatment(1wk, 1mo, 2mo, 3mo, 4mo, 5mo, and 6mo after treatment), and we also measured the Chinese version vision related quality of life questionnaire-25(CVRQoL-25)at 3mo after treatment and compared them separately with the ones measured before treatment to evaluate the efficacy, adverse reactions and the visual related quality of life. <p>RESULTS: Generalized estimation equation results showed that BCVA, CMT and IOP all had differences at different time points(<i>P</i><0.001). A BCVA increase was achieved and CMT decreased in all patients at any time point after the onset of treatment(<i>P</i><0.001). The changes of BCVA and CMT were the largest in the 2mo compared to the baseline(<i>P</i><0.001). The score of CVRQol-25 at 3mo after treatment was significantly higher than that before treatment and then the central retinal thickness decreased and a BCVA increased compared to the baseline level(<i>P</i><0.01). The score of CVRQoL-25 at 3mo was negatively correlated both with the LogMAR BCVA evaluated before treatment and at 3mo after treatment(<i>r</i>s= -0.717, -0.746, all <i>P</i><0.001); Meanwhile, the score of CVRQoL-25 was also negatively correlated with CMT at 3mo after treatment(<i>r</i>s= -0.862,<i> P</i>=0.001). In 19 eyes(63%)of the patients with RVO-ME,a relapse was observed after a follow-up time of 1-3mo and the average recurrence time was(2.8±0.5)mo. In follow-up of 6mo, about(2.3±0.4)intravitreal Ozurdex injections per eye was observed. The increase in IOP was observed at 1wk, 1, 2, 3mo after pretherapy(<i>P</i><0.05). The mean IOP values reached a peak at 2mo after injection, which rose(7.85±0.32)mmHg above the baseline level(<i>P</i><0.05)and decreased to normal at 4mo after treatment. 10% of patients had an elevation in IOP above 25mmHg, which could be medically controlled and 4 eyes(13%)of patients had cataract formation, two of which needed to surgery. <p>CONCLUSION: Ozurdex proved to be efficacious with increase in visual acuity and reduction of central retinal thickness and improve the visual function-related quality of life of RVO-ME patients. After single injection of Ozurdex, visual acuity benefited for 2-3mo. 63% of the patients relapsed at about 3mo after treatment. Adverse reactions associated to the use of Ozurdex include the formation of cataracts and an increase in IOP.

Safety and Efficacy of Dexamethasone Intravitreal Implant in Secondary Macular Edema Patients: A Meta-analysis / 中国药学杂志

OBJECTIVE: To systematically review the safety and efficacy of dexamethasone intravitreal implant (DEX) in secondary macular edema (ME) patients. METHODS: Multiple databases were searched electronically for randomized controlled trials (RCTs) of DEX in secondary ME patients up to April 2019. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Meta-analysis was performed using Rev Man 5.3 software. RESULTS: A total of nine randomized controlled trials involving 1 530 patients were included. There were 737 patients in the experimental group and 793 patients in the control group. DEX was retrieved. Anti-vascular endothelial growth factor (anti-VEGF) or sham injection were used to treat the patients in the control group. The efficacy analysis results showed that the improvement rate of best corrected visual acuity (BCVA) in DEX group was significant higher than the control group in retinal vein occlusion (RVO) patients [MD=-10.59, 95%CI: -13.96--7.23,P=0.01]. The CST/CRT decrease in DEX was significant lower than control group in diabetic macular edema(DME) patients [MD=-63.60, 95%CI: -114.83--12.37,P=0.01], but higher than the control group in RVO [MD=-114.89, 95%CI: -48.68--181.09,P=0.00]. The safty analysis results showed that the incidence of serious adverse events (SAEs) in DEX was significant higher than control group [9.36% (28/299) : 5.23%(19/363), RR=1.94, 95%CI: 1.05-3.59, P=0.04]in RVO. The cataractin DEX was significant higher in RVO [4.87%(22/452) : 0.97% (5/513), RR=5.06, 95%CI: 1.96-13.06, P=0.00] than the control group. CONCLUSION: DEX has better efficacy than anti-VEGF in DME patients. DEX is similar in efficacy but inferior in safety to anti-VEGF in patients with ME secondary to RVO.

Process in the application of dexamethasone vitreous implant / 国际眼科杂志(Guoji Yanke Zazhi)

@#Dexamethasone intravitreal implant is a biodegradable dexamethasone(DEX)0.7mg slow-release implant that progressively dissolves in the vitreous gel. DEX implant now is approved for macular edema(ME)secondary to retinal vein occlusion(RVO), diabetic macular edema(DME)and non-infectious uveitis(NIU). The most common treatment-emergent adverse events are intraocular pressure(IOP)elevation and cataract. Therefore, DEX implant is still second choice level in treatment of RVO-ME and DME. It is reasonable to switch to DEX implant when anti-vascular endothelial growth factor(VEGF)therapy fail. However, DEX implant may be recommended as a first choice for selected cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently. Recent studies suggest dexamethasone implant is safely and effectively improves uveitis-related ME but the role of DEX implant in the management of NIU has yet to be defined. This article reviews the recent progress of DEX implant and focusing on its efficacy and safety.

A Case of Retinal Hemorrhage Following a Dexamethasone Intravitreal Implant

PURPOSE: To report a case of retinal hemorrhage after a dexamethasone (Ozurdex®, Allergan, Irvine, CA, USA) intravitreal implant injection in macular edema (ME) secondary to central retinal vein occlusion (CRVO). CASE SUMMARY: A 60-year-old woman visited our hospital for ME secondary to CRVO in the right eye. Intravitreal bevacizumab injection and vitrectomy was conducted three times, but ME did not improve. Then, dexamethasone intravitreal implant was injected without any problems. Right after the dexamethasone intravitreal implant injection, retinal hemorrhage (2 disc diopter size) was observed in the infero-temporal area on fundus examination. Retinal hemorrhage completely disappeared 1 month after injection without other treatment. CONCLUSIONS: A case of dexamethasone intravitreal implant associated with retinal hemorrhage has not been previously reported in Korea. Althrough retinal hemorrhage was observed, it resolved spontaneously without treatment.

A Case of Anterior Migration of Fragmented Dexamethasone Intravitreal Implant

PURPOSE: To report a case of fragmentation and anterior migration occurred after dexamethasone intravitreal implant (Ozurdex®, Allergan, Irvine, CA, USA) injection in a branch retinal vein occlusion patient. CASE SUMMARY: A 66-year-old male was referred for blurred vision. He received cataract surgery in 1986 and was diagnosed with central retinal vein obstruction in 2011 in the right eye. For treatment of macular edema, dexamethasone intravitreal implant was performed in the right eye. One week after implantation, a fragment of the dexamethasone implant migrated to the anterior chamber with corneal edema and surgical removal was performed immediately. One day after removal, the remaining fragmented implant migrated to the anterior chamber and corneal edema still existed. The fragmented implant was removed with anterior chamber irrigation. After removal, corneal edema improved and visual acuity was recovered. CONCLUSIONS: Anterior migrated dexamethasone implant could induce corneal complications, such as corneal edema and corneal decompensation and might lower the corneal endothelial cell even if immediately removed. We report a case of corneal edema, which was induced by anterior migration of a fragmented dexamethasone implant and recovered with immediate surgical removal.

Dexamethasone Intravitreal Implant in Combination with Laser Photocoagulation for the Treatment of Diffuse Diabetic Macular Edema.

Purpose: To study the efficacy of dexamethasone (DEX) intravitreal implant followed by macular laser after 1-month for diffuse diabetic macular edema (DDME). Methods: Interventional case series of 49 eyes of 33 patients with DDME attending the retina clinic from November 2013 to December 2014. All patients underwent detailed ophthalmic evaluation followed by fluorescein angiography and optical coherence tomography. The sequential macular laser was done after 1-month after DEX implant. All patients had a minimum follow-up of 6 months. Results: Mean age was 58.33 years ± 9.4 years, mean best corrected visual acuity (VA) was 0.5418 logMAR units at presentation improved to 0.4748 at 1-month and maintained 0.4385 at 3 months and 0.4376 at 6 months follow-up (P = 0.01). Mean Central macular thickness was 529.2 μ at presentation reduced to 285.4 μ at 1-month and maintained 296.1 μ at 3 months and 321.1 μ at 6 months follow-up (P = 0.0001). Total macular volume was 11.78 mm3 at presentation reduced to 7.78 mm3 at 1-month and maintained 7.97 mm3 at 3 months and 8.1 mm3 at 6 months follow-up (P = 0.0001). Conclusion: DEX intravitreal implant followed by macular laser showed favorable results by decreasing macular edema and improving VA in DDME, where the role of laser alone is limited.

A Case of Dexamethasone Intravitreal Implant Fragmentation During the Injection Procedure in Central Retinal Vein Occlusion

PURPOSE: We report a case of dexamethasone intravitreal implant (Ozurdex(R); Allergan, Inc.) fragmentation during the injection procedure in macular edema due to central retinal vein occlusion. CASE SUMMARY: A 57-year-old man visited our hospital for visual disturbance in his right eye. The patient's best-corrected visual acuity was 0.02 in the right eye and 1.2 in the left eye. After fundus examination, the patient was diagnosed with central retinal vein occlusion with macular edema, thus bevacizumab was injected in the right eye. However, the macular edema did not improve, and a dexamethasone intravitreal implant was injected in the right eye. Immediately after the dexamethasone intravitreal implant injection, on fundus exam, the drug was observed to be fragmented into 3 pieces without any additional treatment. After 2 months, the patient's best-corrected visual acuity was 0.4 in the right eye and 1.2 in the left eye. Macular edema decreased according to optical coherence tomography. CONCLUSIONS: A case of dexamethasone intravitreal implant fragmentation during an injection procedure has not been previously reported in Korea. Although the drug fragmented, the treatment was effective without complications.