Bobak Bahrami

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance

Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood–retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes.

Anti-VEGF Therapy for Diabetic Eye Diseases

Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness in the working-age population. The identification of vascular endothelial growth factor (VEGF) as a key mediator in the pathogenesis of DR has revolutionized the management of this vision-threatening disease. There is now strong evidence supporting intravitreal anti-VEGF therapy as first line in the management of sight-threatening diabetic macular edema (DME), along with a growing body of evidence to support the use of anti-VEGF drugs for proliferative DR. This review summarizes the role of VEGF in DR, the evidence for anti-VEGF therapy, safety considerations, and the future of anti-VEGF therapy for the management of DR.

Re: Switching therapy from bevacizumab to aflibercept for the management of persistent diabetic macular edema

Purpose To evaluate the visual and anatomical outcomes following switching therapy from bevacizumab to aflibercept in patients with persistent diabetic macular edema (DME).

The role of aflibercept in the management of diabetic macular edema

Diabetic macular edema (DME) represents one of the leading causes of visual impairment in working-age adults. Although there are several proven treatments available for this condition, pharmacotherapy through the use of intravitreal antivascular endothelial growth factor agents has revolutionized the management of DME over the past decade with superior outcomes compared to laser therapy. This review summarizes the pathophysiology and available treatment options for the management of DME, with an emphasis on the efficacy and safety profile of a single particular intravitreal antivascular endothelial growth factor agent, aflibercept.

Heat Shock Protein 70 and Other Heat Shock Proteins in Diseased Retina

Heat shock proteins (HSP) belong to a family of stress-induced proteins essential to cell survival. HSP have multiple protective roles through assistance in protein folding, maintaining mitochondrial homeostasis, suppressing proinflammatory cytokines, resisting ischemic damage and protecting cells from apoptotic and necrotic death. This chapter discusses the important roles of HSP, particularly HSP70 in enhancing the survival of neurons in retinal disease through different pathways. Studies in various retinal cell lines, animal models and human tissue demonstrate altered HSP expression under different stresses and diseases. These findings implicate the critical role of. HSP in the diseased retina as well as providing support for translating the HSP’ cellular defense strategy into therapy to protect and rescue injured retina from different retinal pathology.

Characterization of canonical Wnt signalling changes after induced disruption of Müller cell in murine retina

Abstract Müller cells are the primary glia in the retina, playing a critical role in retinal homeostasis and retinal pathology. This study evaluated the canonical Wnt signalling pathway and its downstream effects on retinal degeneration in a transgenic mouse model of inducible Müller cell disruption. Increased expression of the LacZ reporter gene in the retina suggested Wnt signalling had been activated after induced Müller cell disruption. Activation was validated by observing nuclear translocation of &bgr;‐Catenin. The mRNA expression of 80 Wnt related genes were assessed using real‐time PCR. The Wnt signalling inhibitors Dkk1, Dkk3 and sFRP3 were significantly downregulated. Furthermore, the ubiquitin‐mediated &bgr;‐Catenin proteolysis genes &bgr;‐TrCP and SHFM3, were also significantly downregulated. The downstream target genes of the Wnt signalling, including Fra1, CyclinD2 and C‐Myc were upregulated. The changes of these genes at the protein level were validated by Western blot. Their distributions in the retina were evaluated by immunofluorescent staining. Our findings indicate that Müller cells are involved in retinal Wnt signalling. Activation of Wnt signalling and its downstream target genes may play important roles in photoreceptor degeneration and neovascularization occurring in the retina after induced disruption of Müller cells. HighlightsMüller cell is one of the major cell types involved in retinal Wnt signalling.Multiple cascades of retinal Wnt signalling were activated following Müller cell disruption.Activation of Wnt signalling may play important roles in photoreceptor degeneration and neovascularization.

A meta-analysis of patients with treatment-resistant macular oedema secondary to retinal vein occlusions following switching to aflibercept

To systematically review anatomical and functional outcomes of switching therapy from bevacizumab and/or ranibizumab to aflibercept in patients with persistent macular oedema secondary to retinal vein occlusions (RVO). A systematic search of aflibercept for the treatment of persistent macular oedema secondary to branch and central RVO was performed in EMBASE, PubMed and Cochrane databases prior to June 2017. The main outcome variables described were best‐corrected visual acuity (BCVA) and central macular thickness (CMT). All results were analysed and pooled using random‐effects models with 95% confidence intervals (CI). Eight studies met the inclusion criteria with a total of 137 eyes, incorporating both branch and central RVO. Meta‐analysis demonstrated a nonsignificant change in BCVA at 6 and 12 months following switch to aflibercept (4.40 letters, 95% CI: −3.10 to 11.90, p = 0.25 and 3.10 letters, 95% CI: −1.74 to 7.94, p = 0.21, respectively). Significant improvement in mean CMT was observed after switch to aflibercept at 6 (−256.00 μm, 95% CI: −318.00 to −194.00, p < 0.001) but not 12 months (−118.00 μm, 95% CI: −261.00 to 25.00, p = 0.11). Switching from bevacizumab/ranibizumab to aflibercept may improve persistent macular oedema secondary to RVO. However, there may be a limitation in the potential of visual recovery.

Influence of Retinal Pathology on the Reliability of Macular Thickness Measurement: A Comparison Between Optical Coherence Tomography Devices

BACKGROUND AND OBJECTIVE To evaluate the repeatability, reliability, and comparability of macular thickness measurements between three optical coherence tomography (OCT) machines in healthy eyes, eyes with diabetic macular edema (DME), and eyes with neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS Twenty-three eyes with DME, 26 eyes with nAMD, and 24 healthy eyes as controls were evaluated. Scans were performed using the swept-source Triton (Topcon, Tokyo, Japan), the spectral-domain Cirrus (Carl Zeiss Meditec, Dublin, CA), and the Spectralis (Heidelberg Engineering, Heidelberg, Germany) machines. Scans were evaluated for central macular thickness (CMT), presence of segmentation and fixation imaging artifacts (IA), re-scan reliability, and agreement between machines and groups. RESULTS Mean CMT was significantly different between all OCT machines in all groups (P < .01 for all comparisons). Manually correcting IA did not alter these results. There was good scan repeatability among healthy and DME eyes for each machine, but poor repeatability among the nAMD group with the Spectralis (P = .038). IA were significantly increased in the presence of pathology. CONCLUSIONS There is poor agreement of CMT measurement between OCT machines in healthy eyes and those with DME and nAMD. DME and nAMD have a significant effect on the rate of IA in scans. Care is required when interpreting measurements from different OCT devices in clinical practice and research settings. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:319-325.].

A comparison of macular thickness measurements across three different spectral-domain optical coherence tomography (SD-OCT) machines

Purpose: The aim of this study was to compare the refractive results and perioperative complications of a range of current unifocal intraocular lenses. Method: A prospective cohort study involving 550 cases compared the refractive and visual outcomes of patients receiving Alcon WF/Toric, Zeiss Asphina/Torbi, Hoya 251/351, Tecnis one piece/toric or B&L enVista MX60/MX60T. Surgeries were performed by a single surgeon consecutively. Exclusion criteriawerepostoperative BCVA less than 6/9 where intercurrent opthalmic disease could explain the reduced vision. Patients were reviewed at 1day, 1week and 1month postoperatively. Complications were reviewed and discussed. Results: No statistical significant difference was found in UCVA. Statistical difference was noted between the Hoya 351 and the enVista MX60Tx. The Zeiss lenses gave excellent visual outcomes but had the highest complication rates. The enVista MX60 and Alcon SN6ATx gave the best mix of visual outcome and safety, whilst the HOYA lenses offered the most reliable delivery system. The Tecnis lenses were discontinued due to high predictive error, and the enVista MX60T was discontinued due to poor rotational stability. Conclusion: No definitive answer can be made regarding lens choice. However, this study has led us to use the HOYA lens where lens loading is an issue. Where this is not an issue, we use the enVista MX60 where a non toric lens is required and either the Alcon SN6ATx or Zeiss Torbi where a toric lens is required.