Anti-VEGF and steroid combination therapy relative to anti-VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta-analysis of safety.

The aim of the study was to determine the efficacy and safety of combined anti-VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic review and meta-analysis of peer-reviewed articles reporting on visual, anatomical and adverse outcomes to compare the efficacy and safety of combined intravitreal anti-VEGF/steroids versus anti-VEGF monotherapy for refractory DME. Seven studies (4 RCTs and 3 observational studies) reporting on 452 eyes were included. Our systematic review showed that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared to anti-VEGF monotherapy in six studies. Two studies found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared to anti-VEGF monotherapy. Combination therapy was associated with a higher incidence of IOP-related adverse events (RR = 0.10, 95% CI = [0.02, 0.42], p = 0.002) and cataract-related adverse events (RR = 0.10, 95% CI = [0.01, 0.71], p = 0.02). Our systematic review and meta-analysis of seven studies and 452 eyes revealed that combination therapy of anti-VEGF and steroid intravitreal drugs in the management of treatment refractory DME resulted in superior anatomical outcomes in all but one study. Combination therapy led to superior short-term visual outcomes in two studies, while others reported no difference between treatment groups. Meta-analysis revealed that combination therapy was associated with more adverse events. Future research should provide guidance on the standard definitions for treatment resistance and therapeutic alternatives for DME patients with sub-optimal response to anti-VEGF treatment.

Systematic review of efficacy and meta-analysis of safety of ranibizumab biosimilars relative to reference ranibizumab anti-VEGF therapy for nAMD treatment.

TOPIC: This systematic review and meta-analysis provides a summary of the efficacy and safety of ranibizumab biosimilars relative to reference ranibizumab anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: We conducted systematic searches from January 2003 to August 2022 on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials. We included studies reporting changes in early treatment diabetic retinopathy study-measured best-corrected visual acuity (BCVA), number of patients who lost or gained more than 15 letters in BCVA from baseline, changes in retinal thickness and adverse events between treatment arms. The following studies were excluded: studies that did not report visual outcomes following biosimilar and reference ranibizumab intravitreal injections, study arms combining anti-VEGF agents with laser or steroid injections, sham injections as a control comparator, studies without English full texts and non-comparative, observational study design. RESULTS: Five studies reported on four randomised controlled trials (RCTs) and 1544 eyes at baseline were included in this systematic review and meta-analysis. The studies in our systematic review found no significant differences between reference ranibizumab and ranibizumab biosimilar medications (FYB201, SB11, RanizuRel and Lupin's ranibizumab) for visual and anatomical outcomes. No significant differences were detected between biosimilar and reference ranibizumab for treatment emergent adverse events (risk ratio, RR 1.06, 95% CI (0.91 to 1.23), p=0.45, I2=52%) or IOP-related adverse events with significant heterogeneity (RR 2.59, 95% CI (0.11 to 62.25), p=0.56, I2=76%). CONCLUSION: This systematic review of four RCTs demonstrated no significant difference in visual outcomes, retinal thickness outcomes, as well as meta-analysis of adverse events between biosimilar and reference ranibizumab therapies for nAMD treatment.

Antiviral therapy defiant mixed viral retinitis post hematopoietic allogeneic stem cell transplant.

Cytomegalovirus (CMV) retinitis is an uncommon presentation post allogeneic transplant and can be vision-threatening. Our case demonstrates the occurrence of polymerase chain reaction (PCR) proven mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogeneic stem cell transplant despite multiple prophylactic antiviral therapies, including letermovir, and in the documented absence of CMV DNAemia. A 21-year-old female with acute myeloid leukemia presented with mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogenic transplant. This presentation occurred despite ongoing standard prophylaxis for both of these viruses, as well as following two courses of treatment for CMV viremia, with a documented negative CMV PCR in the blood prior to the presentation with retinitis. The patient was treated with intravenous ganciclovir and subsequently transitioned to oral valganciclovir with durable resolution of the retinitis. We report a rare case of mixed viral retinitis occurring despite multiple antiviral prophylaxes including letermovir and with PCR-documented absence of preceding CMV viremia, in a post-allogeneic stem cell transplant patient, with PCR of the aqueous fluid demonstrating two viral populations. With very little existing literature on either mixed viral retinitis or CMV retinitis during letermovir prophylaxis, this case expands the literature on both topics. CMV retinitis is an uncommon potentially vision threatening presentation post hematopoietic stem cell transplant, and can occur due to early CMV reactivation, low CD4 count, and delayed CD4 lymphocyte recovery. Letermovir has poor CNS and retinal penetration. This case highlights the need for more research on secondary prophylaxis with letermovir.

Eyedrop Instillation Techniques, Difficulties, and Currently Available Solutions: A Literature Review.

Purpose: To review current eyedrop instillation techniques, common difficulties faced by patients instilling eyedrops, available eyedrop assistive devices, and patient education regarding eyedrop instillation. Methods: PubMed, Embase, and Google Scholar were searched from conception until June 2022 for articles on eyedrop instillation difficulties, techniques, tools, and patient education. Results: Instillation involves pulling down the lower eyelids and placing drops on the corneal surface or conjunctival fornix, followed by closing of the eyelids for about 1 min. Examples of techniques include eyelid closure and nasolacrimal obstruction techniques. Patients encounter many difficulties when administering eyedrops, including but not limited to poor visibility, squeezing the dropper bottle, aiming the bottle, and accidentally blinking. However, devices are available that assist with aim and dropper compression-force reduction in eyedrop instillation. These can be particularly useful in patient demographics with diminished manual dexterity or the ability to generate force from their fingers. Furthermore, despite patient education in eyedrop instillation not being a common practice, it has been found that adequate patient education can lead to significant improvement in eyedrop instillation technique. Conclusions: While many factors are associated with poor eyedrop instillation technique, there are many solutions available including assistive devices and proper instillation education.