Refractory Cystoid Macular Edema Research Articles

Successful resolution of refractory cystoid macular edema following tocilizumab therapy in a case of severe recalcitrant juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, with JIA-associated uveitis being the most frequent extra-articular manifestation. If inadequately treated, JIA-associated uveitis can lead to persistent macular edema, potentially causing blinding complications. Tocilizumab, a humanized monoclonal antibody against IL-6, binds to its receptors and inhibits the pro-inflammatory effects of IL-6. This study reports the case of a 30-year-old female with polyarticular JIA-associated uveitis for 24 years, suffering from bilateral refractory cystoid macular edema (CME) resistant to treatments such as corticosteroids, methotrexate, infliximab, adalimumab, and tofacitinib. She received an intravitreal dexamethasone implant in her right eye. Remission of JIA and resolution of CME were achieved with tocilizumab 162 mg subcutaneous injections, combined with low-dose corticosteroids. After 12 doses of tocilizumab, there was no evidence of active uveitis in either eye.

Fluid aspiration from intraretinal cysts for refractory diabetic macular edema

PURPOSE: To report the surgical outcome of fluid aspiration in intraretinal cysts as a novel treatment approach for the refractory cystoid macular edema (CME) associated with diabetic retinopathy. METHODS: This retrospective consecutive case series examined eight patients with refractory CME who underwent intraretinal cyst fluid aspiration using a 38-gauge subretinal infusion needle during pars plana vitrectomy. We reviewed changes in central retinal thickness (CRT), best-corrected visual acuity (BCVA), and central sensitivity among patients followed up for 12 months post-surgery. RESULTS: CRT on optical coherence tomography (μm) significantly improved at 12 months post-surgery (308 ± 99) compared to before surgery (480 ± 141) (P < 0.005). During the follow-up period, CME relapsed in one eye. The BCVA (logarithm of the minimal angle of resolution) at 12 months post-surgery (0.23 ± 0.32, Snellen equivalent: 20/50) was significantly better than the preoperative BCVA (0.39 ± 0.29, Snellen equivalent: 20/63) (P < 0.01). The mean deviation value of central sensitivity did not significantly change between preoperative (-2.5 ± 2.1) and postoperative (-2.2 ± 2.2) assessments (P = 0.07). CONCLUSIONS: Fluid aspiration in intraretinal cysts may be a treatment option for refractory CME in eyes with diabetes.

TOCILIZUMAB RESOLVES REFRACTORY MACULAR EDEMA ASSOCIATED TO RETINITIS PIGMENTOSA.

The aim of this report is to describe the resolution of refractory cystoid macular edema (CME) associated to retinitis pigmentosa (RP) with IV tocilizumab in three patients. Retrospective study of a series of consecutive cases of patients treated with off-label IV tocilizumab (anti IL6) for CME refractory to acetazolamide 250 mg for 3 months. Patients were diagnosed with RP by fundus appearance, electrophysiology, visual fields, and genetic testing. A complete ophthalmic examination including spectral-domain optical coherence tomography was performed. Three patients with RP and CME refractory to acetazolamide 250 mg for 3 months were treated with monthly IV tocilizumab for at least six months.All patients resolved CME and improved visual acuity after the third month of IV tocilizumab, resolving systemic and ocular adverse events related to previous treatments for CME. Tocilizumab was well tolerated with no other adverse events. CME causes visual impairment in RP, but current treatments are usually deficient. Tocilizumab has been successfully used as treatment for refractory CME in uveitis, retinal dystrophies, and autoimmune retinopathies. This article reports, for the first time, the long-term resolution of refractory CME in RP with IV tocilizumab.

Characteristics of macular edema associated with retinal vein occlusion showing poor anatomic response to three loading anti-vascular endothelial growth factor injections: an optical coherence tomography analysis

PurposeTo analyze the clinical features of refractory cystoid macular edema related to retinal vein occlusion associated with the response to three consecutive loading doses of anti–vascular endothelial growth factor.MethodsA retrospective chart review was performed on retinal vein occlusion patients treated by three anti–vascular endothelial growth factor injections. They were divided into a group according to resolution of macular edema in optical coherence tomography (Group 1) and with persistent macular edema (Group 2). We analyzed qualitative and quantitative morphologic features of optical coherence tomography.ResultsWe enrolled a total of 120 eyes from 120 patients (Group 1: n = 54, Group 2: n = 66). The baseline choroidal thickness differed significantly between groups 1 and 2 (290.70 ± 19.58 μm and 311.06 ± 17.87 μm P < 0.001). The presence of Hyperreflective foci (16.70% vs. 36.40% P < 0.001), Disorganization of the retinal inner layers (14.80% vs. 87.90%) and external limiting membrane disruption (16.60% vs. 39.3% P < 0.001) differed significantly. Logistic regression analysis showed that the initial central macular thickness (B = 0.012; P = 0.006), baseline choroidal thickness (B = 0.232; P = 0.016) and presence of hyperreflective foci (B = 1.050; P = 0.019), disorganization of the retinal inner layers (B = 1.132; P = 0.001) and external limiting membrane disruption (B = 1.575; P = 0.012) significantly affected the anti–vascular endothelial growth factor treatment response.ConclusionA thicker sub-fovea choroid and the presence of hyperreflective foci, disruption of the external limiting membrane and disorganization of the retinal inner layers associated with a poorer response to three loading anti–vascular endothelial growth factor injections in macular edema associated retinal vein occlusion.

Fluocinolone acetonide implant scleral fixation for cystoid macular edema in eyes with iris–lens diaphragm disruption

Abstract This is a two-center, case series of three patients with postoperative refractory cystoid macular edema (CME) and disruption of the iris–lens diaphragm, submitted to scleral fixation of fluocinolone acetonide implant. All patients achieved successful CME reduction with visual acuity improvement. The surgical procedure was uneventful in all cases; however, one patient developed hypotony with leakage from the scleral tunnel, which was successfully resolved with reinforcement of the suture and injection of viscoelastics in the anterior chamber. No case of implant migration was observed and patients did not report any visual field disturbances. Our results emphasize this surgical technique as an effective and safe procedure for patients with persistent CME and disruption of the iris–lens diaphragm.

Cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to branch retinal vein occlusion

To demonstrate the long-term effect of cystotomy with or without fibrinogen clot removal for treatment-resistant cystoid macular edema (CME) secondary to branch retinal vein occlusion (BRVO). Retrospective clinical study. We retrospectively analyzed medical records of 22 eyes of 22 patients with treatment-resistant CME secondary to BRVO with 12 months observation after cystotomy with or without fibrinogen clot removal. Patients included 11 women and 11 men. The mean ± SD age was 72.7 ± 10.2 years. LogMAR-converted best corrected visual acuity (BCVA) was statistically better at 12 months after surgery (0.30 ± 0.30) than preoperative BCVA (0.39 ± 0.27) (p = 0.01). The central sensitivity of microperimetry (dB) was maintained during follow-up (preoperative sensitivity: 25.4 ± 4.1, postoperative sensitivity at 12 months after the surgery: 25.9 ± 4.2, p = 0.69). Twelve months after surgery, there was a significant improvement in the central retinal thickness (CRT) on optical coherence tomography (OCT) (303.7 ± 80.1) (μm) compared with the preoperative CRT (524.2 ± 114.8) (p < 0.01). In 12 months, CME recurred in 3 of 22 eyes. The preoperative reflectivity in cystoid cavity on OCT was significantly higher in patients with fibrinogen clot removal (n = 5) than in patients without fibrinogen clot removal (n = 17) (p < 0.01). For treatment-resistant CME secondary to BRVO, Cystotomy with or without fibrinogen clot removal may be one of the treatment options.

Long Term Follow-Up of Tocilizumab in Refractory and Non-Infectious Uveitic Cystoid Macular Edema

Long Term Follow-Up of Tocilizumab in Refractory and Non-Infectious Uveitic Cystoid Macular Edema

Dual therapy for cystoid macular edema treatment after phacoemulsification surgery.

We read with interest the article by Sanders et al.1 that retrospectively compared visual outcomes of patients with clinically significant cystoid macular edema (CME) after cataract surgery to a corresponding case–control group. The cost of treatment and patient-reported outcomes represented additional primary end points. We commend the group on using corrected distance visual acuity, symptoms, and optical coherence tomography findings as a diagnostic criterion that represents a real-world definition of clinically significant pseudophakic CME. Their reported incidence of clinically significant CME of 1.46% is consistent with the literature. As the authors have clearly described, refractory CME can lead to significant perceived visual-related quality of life restrictions and direct financial implications for patients. The paper collaborates a previous report with regard to the risk factors that are associated with refractory CME, diabetes, past vein occlusions, epiretinal membrane, and uveitis.2 Preoperative risk stratification will allow for targeted prophylactic intraoperative antiinflammatory treatment of high-risk eyes. However, the authors' final statement that dual therapy, inclusive of topical nonsteroidal antiinflammatory drug (NSAID) treatment, is standard postoperative care contradicts both the authors' own perioperative protocol and the references used within the paper itself. Within the discussion, the referenced article by Kessel et al. did not in fact indicate a definitive role for NSAIDs in treating clinically significant CME.3 The PREMED study was cited as showing that combined therapy would reduce the incidence of clinically significant CME. The PREMED study did not use visual acuity in its definition of the condition; instead, it used a new definition of “a central subfield thickness increase of 10%” as its definition of CME.4 Of note, the PREMED study reported no difference in the visual acuity at 6 or 12 weeks after the procedure between treatment groups, suggesting the absence of any particular treatment benefit of NSAIDs in regard to vision. The PREMED study also excluded eyes with macular pathology. The lack of high-level evidence for the use of routine prophylactic NSAIDs is supported elsewhere by a previous report by the American Academy of Ophthalmology.5 The use of these references to support the statement that “standard postoperative care is now dual therapy” is therefore unsubstantiated in the literature and in this study.

LONG-TERM EFFECT OF CYSTOTOMY WITH OR WITHOUT THE FIBRINOGEN CLOT REMOVAL FOR REFRACTORY CYSTOID MACULAR EDEMA SECONDARY TO DIABETIC RETINOPATHY.

To show the long-term effect of cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to diabetic retinopathy. Retrospective analyses of the medical records of 30 eyes of 30 patients with refractory cystoid macular edema secondary to diabetic retinopathy who had followed up for 12 months after the surgery were performed. There were 15 men and 15 women. The mean ± SD age was 68.4 ± 7.9 years. The best-corrected visual acuity (logarithm of the minimal angle of resolution) at 12 months after the surgery (0.33 ± 0.25, Snellen equivalent, 20/42) was statistically better than the preoperative best-corrected visual acuity (0.45 ± 0.33, Snellen equivalent, 20/56) (P < 0.01). The central sensitivity on microperimetry (dB) was not statistically changed between preoperatively (24.0 ± 4.9) and 12 months after the surgery (24.1 ± 4.0) (P = 0.75). The central retinal thickness on optical coherence tomography (μm) at 12 months after the surgery (300.3 ± 99.0) was statistically improved compared with the preoperative central retinal thickness (565.6 ± 198.7) (P < 0.01). During the follow-up period, cystoid macular edema relapsed in seven of 30 eyes. The preoperative cystoid cavity reflectivity on optical coherence tomography in patients with fibrinogen clot removal (n = 16) was significantly higher than that in patients without fibrinogen clot removal (n = 14) (P < 0.04). The cystotomy with or without fibrinogen clot removal may be a promising treatment option for refractory cystoid macular edema secondary to diabetic retinopathy.

Escalation to Weekly Adalimumab for the Treatment of Ocular Inflammation

ABSTRACT Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases. Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing. Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months. Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.

Treatment of Refractory Cystoid Macular Edema with Pegylated Interferon Alfa-2A: A Retrospective Chart Review

ABSTRACT Purpose: To determine the efficacy of pegylated interferon alfa-2A in the treatment of refractory inflammatory cystoid macular edema (CME) Methods: Retrospective chart review Results: Treatment with pegylated interferon alfa-2A led to an improvement in CME in all eyes of seven included patients, with a mean decrease in CMT from 478 µm to 310 µm (p < .05). The vision in one patient did not improve due to preexisting retinal atrophy. All other eyes showed improvement in vision, with a mean improvement in best LogMAR visual acuity from +0.59 to +0.28 (p < .05). The treatment effect was sustained with low-dose treatment every 2 weeks or less in the majority of patients. Two patients who stopped interferon treatment given flu-like symptoms and intolerable rash, respectively, showed rapid recurrence of CME. Conclusions: Weekly administration of pegylated interferon alfa-2A is an effective treatment for refractory inflammatory CME, though side effects may limit tolerability in some patients.

Anti-IL6-Receptor Tocilizumab in Refractory and Noninfectious Uveitic Cystoid Macular Edema: Multicenter Study of 25 Patients

Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME. Retrospective case series. Patients with CME secondary to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300μm. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n= 9), Behçet disease (n= 7), birdshot retinochoroidopathy (n= 4), idiopathic (n= 4), and sarcoidosis (n= 1). The ocular patterns were panuveitis (n= 9), anterior uveitis (n= 7), posterior uveitis (n= 5), and intermediate uveitis (n= 4). Most patients had CME in both eyes (n= 24). TCZ was used in monotherapy (n= 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5μm; P= .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P= .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6mg/day vs 3.1 ± 2.3mg/day; P= .002) after 12months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34months. Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.

Usefulness of Intravitreal dexamethasone implant in treatment of persistent cystoid macular edema due to Irvine–Gass syndrome

Introduction: Pseudophakic cystoid macular edema (CME) is one of the commonest causes of visual impairment after uneventful cataract surgery. There is no standardized protocol for pseudophakic CME and cases with refractory or persistent CME remained therapeutic challenge.

Intravitreal Fluocinolone Acetonide (ILUVIEN) Implant for the Treatment of Refractory Cystoid Macular Oedema After Retinal Detachment Repair.

Cystoid macular oedema (CMO) is one of the most frequent postoperative macular complications to cause partial visual recovery after successful retinal detachment (RD) repair. Refractory CMO is difficult to treat and many strategies have been employed with varying degrees of success. We report for the first time the use of ILUVIEN implant to treat refractory CMO after successful RD repair. A 65-year-old female presented with right eye full-thickness macular hole and underwent pars plana vitrectomy, internal limiting membrane peeling and cryotherapy with gas tamponade with 12% C3F8. She subsequently developed right eye macula-on RD and proliferative vitreoretinopathy and required multiple procedures for successful retinal reattachment. Later, she developed CMO that responded to intravitreal triamcinolone injections and intravitreal dexamethasone 0.7-mg implants but recurrence of CMO continued to be a problem. After receiving ILUVIEN intravitreal implant, her visual acuity improved and CMO resolved without recurrence for 13 months. Refractory CMO after RD repair is difficult to treat and in a quarter of cases will not improve without treatment. Our case shows that a single ILUVIEN implant maintained anatomical dry fovea and improved vision. This also demonstrates that ILUVIEN is an effective management strategy to reduce the need for repeated treatments.

Six-month postoperative outcomes of intraoperative OCT-guided surgical cystotomy for refractory cystoid macular edema in diabetic eyes.

PurposeThis study evaluated the outcomes of surgical cystotomy for recurrent diabetic cystoid macular edema (CME).Patients and methodsWe analyzed 20 eyes with a clinical diagnosis of diabetic retinopathy and refractory CME. Release of vitreoretinal adhesion, epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling and cystotomy guided by intraoperative optical coherence tomography (iOCT) were performed in every patient. Pars plana vitrectomy was also performed in 17 patients, 11 of whom also underwent lensectomy and intraocular lens implantation. Central retinal thickness (CRT), central minimum macular thickness (CMMT), macular volume (MV) and best-corrected visual acuity (BCVA) were compared preoperatively and 1 and 6 months post surgery.ResultsCRT, CMMT and MV significantly improved 1 and 6 months post surgery in each group (P<0.01). Significant improvements in BCVA were only observed 6 months post surgery (P<0.01). No intra- or postoperative complications were observed in all patients.ConclusionCRT, CMMT, MV and BCVA significantly improved 6 months following surgical cystectomy. This implies that iOCT-guided cystotomy could be another treatment option for refractory CME in diabetic eyes.

Adalimumab in refractory cystoid macular edema associated with birdshot chorioretinopathy.

To report the clinical outcomes of adalimumab therapy in cases of birdshot chorioretinitis (BCR) with cystoid macular edema (CME) refractory to conventional immunotherapy. This is a retrospective case series of three BCR patients treated with adalimumab for refractory CME. The main outcome measure was central subfield thickness (CST) on optical coherence tomography. Any patients treated with local steroids and/or receiving systemic steroids higher than 40mg prednisolone daily during adalimumab therapy were excluded. At baseline, all patients were receiving systemic corticosteroids and two second-line immunosuppressive agents. The mean duration of treatment with adalimumab was 31.2months (range 17.2-52). The mean CST was 327±112.7μm (mean±SD) at baseline and 256.2±39.7μm at 6months and 235.5±32.5μm at 12months. Adalimumab permitted cessation or reduction in the daily dose of oral prednisolone plus withdrawal of a second-line agent in all patients. In these patients, adalimumab was effective in the treatment of refractory CME.

The effect of intravitreal Ranibizumab for refractory cystoid macular edema after cataract surgery

Objective To evaluate the effect of intravitreal Ranibizumab for refractory pseudophakic cystoid macular edema (CME) after routine senile cataract surgery. Methods From April 2013 to May 2015, 5 patients with refractory pseudophakic CME were treated with intravitreal Ranibizumab injection. Followed up for 3-6 months, visual acuity, retinal morphology and thickness of macula were compared before and after treatment to evaluate the effect. Results After once treatment of intravitreal Ranibizumab, all patients showed better visual acuity and less macular edema without recurrence or complication. Conclusion Intravitreal Ranibizumab is safe and effective for refractory pseudophakic cystoid macular edema. Key words: Ranibizumab, intravitreal; Cataract , age-related; Cystoid macular edema, refractory, pseudophakic

Efficacy of Anti-IL6-Receptor Tocilizumab in Refractory Cystoid Macular Edema of Birdshot Retinochoroidopathy Report of Two Cases and Literature Review

ABSTRACTPurpose: To evaluate tocilizumab (TCZ) efficacy in severe and refractory birdshot chorioretinopathy (BSCR).Methods: Assessment of BSCR patients refractory to conventional immunosuppressive and anti-TNF-α drugs who underwent TCZ therapy.Results: Two HLA-A29 positive patients (man/37 years and woman/38 years; four affected eyes) with BSCR were studied. They had a chronic bilateral posterior uveitis. Patient 1 had been treated with intraocular and oral corticosteroids, cyclosporine A, and infliximab whereas Patient 2 received intravenous methylprednisolone pulses, cyclosporine A, azathioprine, and adalimumab. At TCZ onset they had macular edema (four eyes); visual acuity (VA) impairment (four eyes); vitritis (one eye); and diffuse angiographic signs of vasculitis (periphlebitis) (two eyes). Improvement of VA and OCT was observed following TCZ therapy in both patients. After a follow-up of 18 months (Patient 1) and 10 months (Patient 2), respectively, a corticosteroid sparing effect without any adverse effects was achieved in both cases.Conclusions: TCZ was effective in two patients with BSCR refractory to anti-TNF-α agents.

Intravitreal Implant of Dexamethasone for Treatment of Refractory Cystoid Macular Edema Surgically Induced After Pars Plana Vitrectomy

To evaluate the efficacy and safety of intravitreal implant of Dexamethasone (Ozurdex, Allergan, Irvine, Calif, USA) for the treatment of refractory and chronic cystoid macular edema secondary to PPV and peeling of ERM and internal limiting membrane (ILM) with or without simultaneous cataract surgery.

Short-term safety and efficacy of intravitreal 0.7-mg dexamethasone implants for pseudophakic cystoid macular edema

AimsTo determine the feasibility, safety, and clinical efficacy of intravitreal 0.7-mg dexamethasone implants (Ozurdex) in patients with refractory cystoid macular edema after uncomplicated cataract surgery. Methods and materialsIn this study, 11 eyes of 11 patients affected by pseudophakic cystoid macular edema refractory to medical treatment were treated with a single intravitreal injection of a dexamethasone implant. Follow-up visits involved Early Treatment Diabetic Retinopathy Study visual acuity testing, optical coherence tomography imaging, and ophthalmoscopic examination. ResultsThe follow-up period was six months. The mean duration of cystoid macular edema before treatment with Ozurdex was 7.7months (range, 6–10months). The baseline mean best corrected visual acuity (BCVA) was 0.58±0.17 logarithm of the minimum angle of resolution (logMAR). The mean BCVA improved to 0.37±0.16logMAR (p=0.008) and 0.20±0.13logMAR (p=0.001) after 1 and 3months, respectively. At the last follow-up visit (6-month follow-up), the mean BCVA was 0.21±0.15logMAR (p=0.002). The mean foveal thickness at baseline (513.8μm, range, 319–720μm) decreased significantly (308.0μm; range, 263–423μm) by the end of the follow-up period (p<0.0001). Final foveal thickness was significantly correlated with baseline BCVA (r=0.57, p=0.002). No ocular or systemic adverse events were observed. ConclusionsShort-term results suggest that the intravitreal dexamethasone implant is safe and well tolerated in patients with pseudophakic cystoid macular edema. Treated eyes had revealed a significant improvement in BCVA and decrease in macular thickness by optical coherence tomography.