|Year : 2021 | Volume
| Issue : 3 | Page : 370-372
Jincy Mariya Paul
Department of Ophthalmology, Government Medical College, Thrissur, Kerala, India
|Date of Submission||23-Sep-2021|
|Date of Acceptance||23-Sep-2021|
|Date of Web Publication||08-Dec-2021|
Jincy Mariya Paul
Department of Ophthalmology, Government Medical College, Thrissur, Kerala
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Paul JM. Journal Review. Kerala J Ophthalmol 2021;33:370-2
| Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend for Macular Edema in Central Retinal Vein Occlusion: The Centera Study|| |
Jean-François K, Larsen M, Eter N, Bailey C, Wolf S, Schmelter T, et al. Efficacy and safety of intravitreal aflibercept treat-and-extend for macular edema in central retinal vein occlusion: The CENTERA study. Am J Ophthalmol 2021;227:106-15.
Retinal vein occlusion constitutes a large burden of retinal vascular disease globally. Macular edema and macular ischemia are the causes for reduction in vision in central retinal vein occlusion (CRVO), branch retinal vein occlusion as well as hemiretinal vein occlusion. CRVO could be ischemic as well as nonischemic. Although several treatment options existed conventionally including retinal laser photocoagulation, intravitreal corticosteroid injections and implants, and intravitreal anti-vascular endothelial growth factors (anti-VEGFs), there has been a paradigm shift toward the use of anti-VEGF agents consistently over the years.
The effectiveness of intravitreal anti-VEGF therapy is well established in the management of macular edema secondary to retinal vein occlusions. There is, however, a wide variation in the response to treatment among patients in terms of resolution of macular edema and improvement in best-corrected visual acuity. There may be good or early responders as well as partial or nonresponders.
The anti-VEGF agents could be administered using different dosing intervals. Most standard clinical trials in the field of anti-VEGF therapy used a fixed-dosing regimen, which is predictable and straightforward for both the treating doctor and the patient. The associated high, clinic and patient burden (especially with monthly visits), and risks of either over-or undertreatment, is a major issue with fixed-dosing intervals.
In pro re nata (PRN) regimens, patients are treated on disease reactivation in an effort to reduce injection frequency and costs. Patients typically follow a monthly schedule of clinic visits, where the decision to re-treat at each visit is based on a set of prespecified criteria, as determined by the treating doctor (e.g., visual acuity [VA] and optical coherence tomography/fluorescein angiography assessments). Outcomes obtained with this regimen depend largely on the re-treatment criteria employed and how closely these are adhered to. This is most commonly employed.
Both these regimens do not factor in the patient response.
A treat-and-extend regimen is a more proactive and individualized approach to treatment, with the goal of preventing disease recurrence. This tailors the dosing interval based on patient response as well. The drug is administered at every scheduled visit, despite visual or anatomic status on the day. The interval between each visit is either increased or decreased according to the anatomic and VA status, to determine the maximum recurrence-free interval. The need for interim monitoring is minimized, which reduces the number of appointments per patient. Post hoc analyses of COPERNICUS and GALILEO supported the implementation of proactive treatment to prevent deterioration of functional and anatomic outcomes.
The aim of the CENTERA study was to assess the efficacy and safety of intravitreal aflibercept (IVT-AFL) administered in a treat-and-extend dosing regimen in patients with macular edema secondary to CRVO, as large-scale studies evaluating treat-and-extend regimens of IVT-AFL for the treatment of macular edema secondary to CRVO are lacking. Furthermore, even in studies demonstrating the benefit of IVT-AFL in the treatment of macular edema secondary to CRVO, the post hoc assessment of different dosing subgroups showed destabilization of disease with PRN dosing.
CENTERA was an open-label, multicentric, Phase 4 clinical trial of 162 patients, with center involving macular edema secondary to CRVO lasting <3 months. In this single-arm study, the patients received 2-mg IVT-AFL injections at baseline and every 4 weeks until disease stability criteria were met or until week 20, whichever occurred first. Starting at week 8, the re-treatment interval was adjusted by 2-weekly increments to maintain stable functional and anatomic outcomes.
The study found that 65.6% of patients gained ≥15 letters, from baseline to week 76. In the treat-and-extend phase, only 45.0% of patients achieved a mean treatment interval of ≥8 weeks. Post hoc analysis demonstrated that 63% and 68% of patients achieved a last and next planned treatment interval of ≥8 weeks, respectively, and a last actual treatment interval of ≥8 weeks was achieved by 63.1% of patients. The mean BCVA was 51.9 letters at baseline and 72.3 letters at week 76 (+20.3 letters). The mean central retinal thickness decreased from 759.9 μm at baseline to 265.4 μm at week 76 (−496.1 μm). These outcomes were comparable to other studies of IVT-AFL using fixed-dosing or PRN regimens.
The post hoc analysis indicated that longer treatment intervals would have been achieved with longer study duration.
Ninety-three percent of patients in this study, however, had nonischemic CRVO. Although other studies such as the COPERNICUS and VIBRANT show the efficacy of IVT-AFL in ischemic CRVO as well, it remains to be studied whether the treat-and-extend dosing regimen would give similar results.
A high statistical power of ≥90%, inclusion of a broad range of baseline visual function (24-73 ETDRS letters), and early initiation of treatment were among the strengths of the study. Being a single-arm study with no active comparator, interpretation of the results is potentially limited. Furthermore, analysis of the last and next planned treatment intervals was post hoc in nature, which again limited the interpretation of the data. One hundred and thirty-one patients (80.9%) reported at least two treatment-emergent adverse events (TEAEs) during the study, and these TEAEs were predominantly mild or moderate in severity. The study does not discuss further regarding the benefit of a treat-and-extend regimen in terms of safety.
The authors concluded that clinically meaningful and significant improvements in functional and anatomic outcomes were achieved with IVT-AFL administered using a treat-and-extend regimen in patients with macular edema secondary to CRVO. The treatment intervals could also be extended beyond 8 weeks in many patients.
Studies exploring associated systemic risk factors such as diabetes mellitus and hypertension could further enhance our understanding regarding poor or nonresponse to treatment and help further modulate the treat-and-extend regimens. This would help reduce the financial burden on patients, especially in a setting like ours.
| Outcomes of Gonioscopy-Assisted Transluminal Trabeculotomy in Pseudoexfoliative Glaucoma: 24-Month Follow-Up|| |
Sharkawi E, Lindegger DJ, Artes PH, Lehmann-Clarke L, El Wardani M, Misteli M, et al. Outcomes of gonioscopy-assisted transluminal trabeculotomy in pseudoexfoliative glaucoma: 24-month follow-up. Br J Ophthalmol 2021;105:977-82.
Glaucoma is a progressive optic neuropathy that causes ganglion cell apoptosis and visual field loss, multifactorial in origin.
Pseudoexfoliation syndrome is an age-related systemic microfibrillopathy, characterized by progressive accumulation and gradual deposition of extracellular gray and white material over various tissues. It is one of the most common causes of secondary glaucoma and is associated with a worse prognosis than primary open-angle glaucoma showing reduced response to medications and faster progression, often requiring a surgical intervention.
Reduction of intraocular pressure (IOP) has been shown to slow glaucomatous progression, and IOP is the primary treatment target. Both glaucoma and its treatment can significantly affect the quality of life. Topical or oral IOP-lowering therapy, laser trabeculoplasty, and incisional glaucoma surgery (trabeculectomy and glaucoma drainage device implantation) formed the conventional treatment modalities.
The concept of minimally invasive glaucoma surgeries is revolutionizing the management of glaucoma. These techniques do not form a bleb, using an ab interno approach, and target the trabecular meshwork (TM), the primary anatomic structure responsible for aqueous outflow resistance.
Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive surgical technique in which a suture or catheter is used to bypass the TM circumferentially. The aqueous humor is thus shunted via the opened up TM, into the collector channels and flows out through the episcleral veins. The ab interno GATT procedure reports a remarkably good success rate, while negating several side effects of the earlier conventional scleral flap surgeries.
GATT being a relatively recent development in glaucoma management, the aim of this study is to present the outcomes of an ab interno GATT in eyes with pseudoexfoliation glaucoma (PXG) with a follow-up of up to 2 years.
This was a prospective, interventional, noncomparative case series and enrolled a total of 103 eyes from 84 patients with PXG. They showed progression of glaucoma despite maximal tolerated medical therapy. A 360°, ab interno trabeculotomy with gonioscopic assistance using either a 5.0 polypropylene suture or an illuminated microcatheter was performed. They were followed up to 24 months after surgery.
Main outcome measures were IOP, number of antiglaucoma medications, success rate (IOP reduction ≥20% from baseline or IOP between 6 and 21 mmHg, without further glaucoma surgery) and complication rate recorded at day 1, week 1, week 3, week 6, month 3, month 6, month 12, month 18 and month 24, or more frequently if clinically indicated by the physician.
Combined cataract surgery with GATT was performed in 50 eyes while the remaining 53 eyes were already pseudophakic. Postoperative IOP was significantly lower than baseline at all study time points for both groups. This reduction was statistically significant. The mean preoperative IOP was 27.1 (95% confidence interval [CI]: 25.5–28.7) mmHg using 2.9 (standard deviation: 1.1) glaucoma medications. An IOP reduction of 52% with a mean IOP of 14.1 (95% CI: 12.1–16.0) mmHg was achieved on postoperative day 1, with all glaucoma medications being stopped unless there was a postoperative IOP spike or steroid response.
The overall success rate was 89.2% at 24 months. Twenty-five cases had isolated IOP spikes, but there was only one case with transient hypertony. The overall complication rate was 2.9%. Low complication rate with a greater reduction of IOP and the cost-effectiveness of GATT, maintains the quality of life of the patient. The combination of cataract surgery and GATT maintained the same effectiveness as GATT alone in pseudophakic patients. There were six cases of partial trabeculotomy as well which were also successful.
The noncomparative design, the mid-term follow-up of up to 24 months, and the decreasing study pool due to some patients having the procedures performed <2 years before the end of this study were some of the limitations of this study. The adequacy of the sample size, therefore, is thus debatable. A switch from catheter-GATT to suture-GATT was made 1 year into the study due to economic reasons, and this limited the possibility of comparison between the groups. The success of the procedure depends on the anatomical integrity of the collector channels which cannot be assessed preoperatively, and this is a limitation of GATT. Furthermore, the number of patients having to be maintained on antiglaucoma medications postsurgery and the reasons for the same have not been discussed in detail. However, the requirement for antiglaucoma medications has definitely decreased at 24 months, which has been considered to be a factor pointing toward success of procedure.
The authors concluded that GATT safely and effectively lowers IOP in PXG and could even be considered as a suitable first-line treatment option given the relatively aggressive nature of PXG. The cost-effectiveness of the procedure can further be enhanced by using a polypropylene suture.
Early intervention using GATT achieves early control of IOP. Due to its ab interno nature, it leaves the option of a further conventional surgery like trabeculectomy with or without a drainage device later if IOP control fails in future.
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Conflicts of interest
There are no conflicts of interest.