Use of a dexamethasone implant to treat macular edema following pars plana vitrectomy and removal of the primary epiretinal membrane.

PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of an intravitreal dexamethasone (DEX) implant for the treatment of macular edema (ME) following pars plana vitrectomy (PPV) and removal of the primary epiretinal membrane (ERM) and to assess the impact of the integrity of the ellipsoid zone (EZ) and disorganization of the retinal inner layer (DRIL) grade on visual and anatomical outcomes. METHODS: Forty-two pseudophakic patients who developed ME following PPV and removal of the primary stage 2-3 ERM were included. Patients were divided into two groups when ME was diagnosed via spectral domain optic coherence tomography (SD-OCT). In the DEX group (n = 22), DEX was implanted for the treatment of ME. In the control group (n = 20), only observation was conducted, without any treatment. The best-corrected visual acuity (BCVA) and macular thickness (MT) of the two groups were compared at baseline and 1, 6, and 12 months after DEX implantation. The effects of OCT parameters such as EZ integrity and DRIL grade were also evaluated in terms of decreases in MT and increases in VA in the treatment of ME with DEX implantation. Intraocular pressure (IOP), number of DEX implantations and adverse effects were also recorded. RESULTS: While a statistically significant increase in the mean BCVA was observed in the DEX group (p < 0.001 at months 1, 6, and 12, respectively), no such increase was detected in the control group (p = 0.169, p = 0.065, and p = 0.058 at months 1, 6 and 12, respectively) compared with the baseline. A statistically significant decrease in the mean MT was observed in the DEX group (p < 0.001 at months 1, 6, and 12); however, no significant difference was observed in the control group (p = 0.081, p = 0.065, and p = 0.054 at months 1, 6 and 12, respectively) compared with the baseline. Significant differences were found between the two groups in terms of the increase in BCVA (p < 0.01) and decrease in MT (p < 0.01) at all visits, with the outcomes being more favorable in the DEX group. A statistically significant relationship was found between the increase in VA and EZ integrity and DRIL grade in both groups. Ten patients (45.4%) received two injections of DEX during the follow-up. An increase in IOP was observed in five patients (22.7%) who were treated with topical antiglaucomatous drops. No significant side effects were observed. CONCLUSION: DEX implantation was found to be effective and safe for the treatment of ME following PPV and primary ERM removal, although some eyes may require repeated injections to achieve visual and anatomical success. Additionally, a relationship was found between EZ integrity, DRIL grade and visual-anatomical outcomes.

[Clinical observation of the subthreshold micropulse laser combined with ranibizumab for treatment of diabetic macular edema].

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)µm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)µm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

Management of diabetic ocular complications: from cellular insights to community strategies.

The editorial outlines an integrated approach to managing diabetic ocular complications, combining advanced scientific research with practical public health strategies to improve the prevention, diagnosis, and treatment of diabetic retinopathy and macular edema globally.

Anti-Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. METHODS: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. RESULTS: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of -0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. CONCLUSIONS: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.

Current management options for the treatment of refractory postoperative cystoid macular edema: A systematic review.

Post-operative cystoid macular edema (PCME) is an important complication following intraocular surgery that often resolves spontaneously without treatment. In some cases, PCME may persist despite initial medical therapy, which can adversely impact visual outcomes. Various topical, intraocular and systemic treatments exist for the prevention and management of cystoid macular edema; however, there is no consensus on treatment of refractory cases in the postoperative setting. In accordance with the PRISMA guidelines, we systematically reviewed 68 articles describing management options and their outcomes for treatment-resistant cases of PCME. The most commonly reported treatments included steroid (39 studies) and biological-based (17 studies) therapies. We provide an overview of the treatment options for refractory PCME.

Protocol for the treatment of cystoid macular edema secondary to retinitis pigmentosa and other inherited retinal dystrophies.

Inherited retinal dystrophies (IRD) are the leading cause of legal blindness in the working population. Cystic macular edema (CME) is one of the treatable causes of visual loss, affecting up to 50% of the patients. A bibliographic review has been carried out combining "inherited retinal dystrophy", "retinitis pigmentosa", "macular oedema" and a diagnostic-therapeutic protocol according to the levels of evidence and recommendations of the "US Agency for Healthcare Research and Quality". This protocol has been discussed in the monthly meetings of the XAREA DHR group with the participation of more than 25 ophthalmologists, creating a consensus document. The etiology of CME is multifactorial: dysfunction of the blood-retinal barrier, retinal pigment epithelium, and Müller cells, inflammation, and vitreous traction. OCT is the test of choice for the diagnosis and follow-up of CME associated with IRD. The drugs with the highest degree of scientific evidence are carbonic anhydrase inhibitors (IAC). Intravitreal corticosteroids, anti-VEGF, and vitrectomy with peeling of the internal limiting membrane do not have sufficient evidence. A treatment scheme is proposed for the CME in IRD in adults, another for pediatric patients and another for IRD and cataract surgery. Oral and topical IACs are effective in the treatment of CME secondary to IRD. Treatment with corticosteroids, anti-VEGF, and vitrectomy are second-line options. Randomized clinical trials are required to establish the therapeutic scale in these patients.

Optical coherence tomography in the management of diabetic macular oedema.

Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1 mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.

Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). MATERIALS AND METHODS: A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies. RESULTS: A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events. CONCLUSIONS: Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.

Diabetic Macular Edema - Diagnostics and Treatment Guidelines.

Together with diabetic retinopathy, diabetic macular edema (DME) ranks among the most common causes of severe loss of vision in working adults. Due to recent developments in imaging methods, new classification schemes of DME have been created. In addition to this, new treatment options have been introduced (new intravitreal drugs as well as treatment protocols). At the same time laser, surgical as well as combination therapy is still available. In this paper we evaluate the current knowledge about DME diagnostic and treatment options and formulate recommended guidelines for the management of DME.

Diabetic Retinopathy ­ Diagnostics and Treatment Guidelines

Diabetic retinopathy is one of the most common complications of diabetes mellitus and represents a serious health, social and economic problem. With the expected increase in the number of patients with diabetes, it is becoming the leading cause of severe vision loss in the working-age population.  The presented guidelines summarize the current knowledge about this disease in order to standardize and update the procedures for the diagnosis, classification and treatment of diabetic retinopathy.

Pediatric Pars Planitis: A Review.

PURPOSE: To provide an overview of pediatric pars planitis. METHODS: Narrative literature review. RESULTS: Pars planitis refers to the idiopathic subset of intermediate uveitis in which there is vitritis along with snowball or snowbank formation occurring in the absence of an associated infection or systemic disease. It is thought to be a T-cell mediated disease with a genetic predisposition. Pars planitis accounts for 5-26.7% of pediatric uveitis cases. Presentation is commonly bilateral but asymmetric, often with insidious onset of floaters and blurred vision. Although pars planitis is known to be a benign form of uveitis in most cases, severe complications secondary to chronic inflammation may arise, with cystoid macular edema being the most common cause of visual morbidity. Mild vitritis in the absence of symptoms, vision loss, or macular edema may be observed. Patients with severe vitritis and/or associated vision-threatening complications require prompt aggressive treatment. A stepladder approach including corticosteroids, immunosuppressive agents, anti­tumor necrosis factor­alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. CONCLUSION: Timely diagnosis and adequate treatment of pediatric pars planitis and associated complications are crucial in order to improve visual outcomes.

From randomised controlled trials to real-world data: Clinical evidence to guide management of diabetic macular oedema.

Randomised clinical trials (RCTs) are generally considered the gold-standard for providing scientific evidence for treatments' effectiveness and safety but their findings may not always be generalisable to the broader population treated in routine clinical practice. RCTs include highly selected patient populations that fit specific inclusion and exclusion criteria. Although they may have a lower level of certainty than RCTs on the evidence hierarchy, real-world data (RWD), such as observational studies, registries and databases, provide real-world evidence (RWE) that can complement RCTs. For example, RWE may help satisfy requirements for a new indication of an already approved drug and help us better understand long-term treatment effectiveness, safety and patterns of use in clinical practice. Many countries have set up registries, observational studies and databases containing information on patients with retinal diseases, such as diabetic macular oedema (DMO). These DMO RWD have produced significant clinical evidence in the past decade that has changed the management of DMO. RWD and medico-administrative databases are a useful resource to identify low frequency safety signals. They often have long-term follow-up with a large number of patients and minimal exclusion criteria. We will discuss improvements in healthcare information exchange technologies, such as blockchain technology and FHIR (Fast Healthcare Interoperability Resources), which will connect and extend databases already available. These registries can be linked with existing or emerging retinal imaging modalities using artificial intelligence to aid diagnosis, treatment decisions and provide prognostic information. The results of RCTs and RWE are combined to provide evidence-based guidelines.

Microinvasive pars plana vitrectomy combined with internal limiting membrane peeling versus anti-VEGF intravitreal injection for treatment-naïve diabetic macular edema (VVV-DME study): study protocol for a randomized controlled trial.

BACKGROUND: Diabetic macular edema (DME) is the main cause of vision loss in diabetic patients. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injection stands as the first-line therapy for DME. However, some patients exhibit insufficient response to anti-VEGF agents and often require multiple injections, imposing psychological and economic burdens. While microinvasive pars plana vitrectomy (PPV) has been shown to be safe and effective in treating refractory DME, scant research has explored its application to treatment-naïve DME. The purpose of this study is to determine whether early PPV combined with internal limiting membrane (ILM) peeling can lessen the therapeutic burden of DME patients, prevent vision loss, and maintain long-term stabilization of diabetic retinopathy. METHODS: This is a single-center, prospective, parallel-group, non-inferiority randomized controlled trial involving 102 DME participants. Participants will be randomly assigned to either the study group (PPV combined with ILM peeling) or the control group (conbercept intravitreal injection (IVC)) at a 1:1 ratio, with a scheduled follow-up at 12 months post-operation. Comparative analysis of results between the two groups will be conducted at months 1, 3, 6, and 12 after the intervention. The primary outcomes involve evaluating the changes in central subfield thickness (CST) and best corrected visual acuity (BCVA). The secondary outcomes include assessment of optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers, re-treatment and adverse events rates, diabetic retinopathy (DR) development, cost-effectiveness analysis, and vision-related quality of life (VRQL). DISCUSSION: Some patients do not respond well to anti-VEGF drugs and repeated intravitreal injections increase the treatment burden for patients. The VVV study aims to explore whether PPV combined with ILM peeling could become an initial treatment option for treatment-naïve DME patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05728476. Registered on 15 February 2023.

Real-world treatment patterns and economic burden of post-cataract macular edema.

BACKGROUND: Post-cataract macular edema (PCME) is a condition that can occur in patients following cataract surgery without risk factors and complications. Although 80% of patients experience spontaneous resolution after 3 to 12 months, in persistent cases, it can lead to permanent vision loss if left untreated. There are currently no standardized treatment guidelines for PCME, and there have been limited studies showing the impact of PCME on annual Medicare spending and ophthalmology-related outpatient visits per case compared to those without the complication. This study aims to evaluate real-world treatment patterns and the economic burden of patients with PCME. METHODS: This retrospective claims analysis identified patients from the IBM® MarketScan® Commercial and Medicare Supplemental databases. Patients with (n = 2430) and without (n = 7290) PCME 1 year post cataract surgery were propensity score matched 1:3 based on age, geographic region, diabetes presence, cataract surgery type, and Charlson Comorbidity Index. Treatment pattern analysis for each PCME patient summarized the distribution of medications across lines of therapy. Economic burden analysis compared the mean number and costs of eye-related outpatient visits, optical coherence tomography imaging scans, and ophthalmic medications between the 2 groups using linear regression models. RESULTS: Treatment pattern analysis found 27 different treatment combinations across 6 treatment lines. The most common first-line treatments were topical steroid drops (372 [30%]), topical nonsteroidal anti-inflammatory drug drops (321 [27%]), and intraocular or periocular injectable steroids (189 [15%]). Compared to match controls, PCME patients averaged 6 additional eye-related outpatient office visits (95% CI: 5.7-6.2) resulting in an additional $3,897 (95% CI: $3,475 - $4,319) in total costs. Patients filled 3 more ophthalmology-related outpatient prescription medications (95% CI: 2.8-3.2), adding $371 in total cost (95% CI: $332 - $410). CONCLUSIONS: PCME treatment patterns showed wide clinical variability in treatments and time, specifically regarding injectable treatments and combination therapy. Additionally, significantly higher healthcare resource use and economic burden were found for both patients and payers when comparing PCME patients to non-PMCE controls. These results highlight the need for treatment standardization and demonstrate that interventions targeted at preventing PCME may be valuable.

Current Treatments for Diabetic Macular Edema.

Diabetic retinopathy is a major retinal disorder and a leading cause of blindness. Diabetic macular edema (DME) is an ocular complication in patients with diabetes, and it can impair vision significantly. DME is a disorder of the neurovascular system, and it causes obstructions of the retinal capillaries, damage of the blood vessels, and hyperpermeability due to the expression and action of vascular endothelial growth factor (VEGF). These changes result in hemorrhages and leakages of the serous components of blood that result in failures of the neurovascular units (NVUs). Persistent edema of the retina around the macula causes damage to the neural cells that constitute the NVUs resulting in diabetic neuropathy of the retina and a reduction in vision quality. The macular edema and NVU disorders can be monitored by optical coherence tomography (OCT). Neuronal cell death and axonal degeneration are irreversible, and their development can result in permanent visual loss. Treating the edema before these changes are detected in the OCT images is necessary for neuroprotection and maintenance of good vision. This review describes the effective treatments for the macular edema that are therefore neuroprotective.

[Diagnosis, treatment and monitoring of diabetic eye disease (Update 2023)]. / Diagnostik, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung (Update 2023).

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these disorders correlates with disease duration and quality of metabolic control. Regular ophthalmological examinations are needed to prevent sight-threatening advanced stages of diabetic eye diseases.