Systematic Literature Reviews Comparing the Long-Term Safety Outcomes for the Port Delivery System with Ranibizumab (PDS) Versus Other Ocular Implants.

OBJECTIVES: To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera. METHODS: Systematic literature reviews were conducted to determine the long-term (≥ 18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion). RESULTS: Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0-5.0%) of study eyes in clinical trials and 1.3% (0.0-14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0-22.8%) and 2.2% (0.9-4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants. CONCLUSIONS: The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice. TRIAL REGISTRATION: PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129.

One-Year Functional and Morphological Prognosis After Intravitreal Injection Treatments According to Different Morphological Patterns of Diabetic Macular Edema in Real-Life: MARMASIA Study Group Report No.13.

PURPOSE: To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy. METHODS: In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups. RESULTS: 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups (p = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 (p = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups (p = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively (p > .05). The groups had no significant difference in mean CMT at month 12 (p = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 (p = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 (p = 0,014 and p = 0,017). CONCLUSIONS: In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.

Calculated Drug Concentrations in Currently Available Intravitreal Therapies: Determination of Dilution Factor and Deviation From Recommended Doses.

In ophthalmology, intravitreal therapies are currently not personalized/customized and are not adjusted to the individual vitreous volume. With reference to the recently published calculation formula for a more accurate estimation of the vitreous body, we determined the dose of intravitreal medication for different vitreous volumes and compared them with the average volume. Using the axial length of the eye, the formula for the vitreous volume exact (VIVEX) can provide a more accurate indication of the vitreous volume in individual cases than an assumed standard volume of 4 mL. The concentration of active substances in small eyes may be twice as high as that in normal-sized emmetropic eyes. In contrast, large eyes may show less than half of the recommended drug concentration. The calculated concentrations of the investigated intravitreal drugs in small and large eyeballs showed impressive differences with large deviations from the recommended doses. Further systematic studies should follow to find out whether this has any impact on the effectiveness or side effects of the injected drugs.

Association of serum lipid profile and other systemic risk factors with retinal hard exudates in diabetic retinopathy.

PURPOSE: Diabetic macular edema is one of the leading causes of vision loss across the world. Hard exudates at the macula can lead to structural abnormalities in the retina leading to irreversible vision loss. Systemic dyslipidemia and other modifiable risk factors when identified and treated early may help prevent substantial vision loss. The purpose of this study was to study the association between serum lipid levels and other systemic risk factors like hemoglobin, HbA1c, and serum creatinine with hard exudates and macular edema in patients with diabetic retinopathy. METHODS: It is a prospective cross-sectional study conducted in a tertiary health care center in South India. 96 patients having diabetic retinopathy with hard exudates were included. Modified Airlie house classification was used to grade the hard exudates. Blood investigations including serum lipid profile, hemoglobin, HbA1c, and serum creatinine were carried out. Central subfield macular thickness was measured using optical coherence tomography. RESULTS: 96 patients of type II DM with diabetic retinopathy were divided into three groups of hard exudates. A statistically significant correlation was observed between the severity of hard exudates and total cholesterol (p = 0.00), triglycerides (p = 0.00), LDL (p = 0.00), and VLDL (p = 0.00). HbA1c levels showed a statistically significant correlation with the severity of hard exudates (p = 0.09), no significant correlation was noted between hard exudates and hemoglobin levels (p = 0.27) and with serum creatinine (p = 0.612). A statistically significant association between CSMT and hard exudates (p = 0.00) was noted. CONCLUSION: In our study, we concluded that the severity of hard exudates is significantly associated with increasing levels of serum total cholesterol, triglycerides, LDL, VLDL, and HbA1c levels in type II DM patients presenting with diabetic retinopathy. The increasing duration of diabetes is significantly associated with increasing severity of hard exudates. Central subfield macular thickness increases with increasing severity of hard exudates in diabetic retinopathy.

Effectiveness of Suprachoroidal Injection of Triamcinolone Acetonide in Diabetic Macular Edema Following Pars Plana Vitrectomy Using a Modified Custom Microneedle.

Purpose: The present study evaluated the efficacy of suprachoroidal injection of Triamcinolone Acetonide (SCTA) in diabetic macular edema (DME) following pars plana vitrectomy (PPV) using a modified microneedle. Patients and methods: A prospective interventional study was conducted on 60 eyes of 60 patients with centrally involved diabetic macular edema following pars plana vitrectomy (PPV). SCTA was performed at the baseline and repeated after 3 months in case of persistent subretinal or intraretinal fluid, central macular thickness (CMT) more than 300 µm or visual loss by more than one line of the Snellen chart. Results: The present study detected significant reduction of the CMT from 498.3 ± 94.8 µm at the baseline to 212.3 ± 11.9 µm after 12 months of injection with p < 0.001 and a significant improvement of best corrected visual acuity (BCVA) from 1 (0.9-1.2) at the baseline to 0.5 (0.3-0.7) after 12 months of injection with p < 0.001. The intraocular pressure (IOP) increased significantly after 3 months of injection with p < 0.001 and then gradually declined to its normal level after 6 months. Inner segment/outer segment (IS/OS) disruption was the only significant predictor of the final CMT; however, the number of injections, IS/OS disruption, baseline BCVA and the HbA1C level were the significant predictors of the final BCVA after injection. Conclusion: Suprachoroidal injection of TA using this microneedle resulted in significant anatomical and functional improvement in previously vitrectomized diabetic macular edema patients with no recorded ocular or systemic adverse events.

Aflibercept or ranibizumab for diabetic macular edema.

Background: Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. Methods: This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Results: Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Conclusions: Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

The Management of Two Cases with Retinal Arterial Macroaneurysm by Anti-Vascular Endothelial Growth Factor.

Introduction: We report on one case of age-related macular degeneration and one case of diabetic macular edema with concomitant retinal arterial macroaneurysm (RAM) that were treated with anti-vascular endothelial growth factor (VEGF) intravitreal injections. Case Presentation: Case 1 involved a 71-year-old woman with a 30-year history of diabetes who was undergoing dialysis. Pretreatment visual acuity in the right eye was 0.4. Fundus fluorescein angiography (FA) showed that numerous microaneurysms and RAM were located at a distance of two papillary diameters from the macular area. Diabetic macular edema was diagnosed. After 12 anti-VEGF injections, the macular edema resolved, microaneurysms decreased, and the RAM also disappeared. Visual acuity in the right eye improved to 0.7. Case 2 involved an 81-year-old woman receiving treatment for disorders including hypertension and dyslipidemia. Pretreatment visual acuity in the right eye was 0.03. And vitreous hemorrhage was present. After one ranibizumab intravitreal injection, the fundus became clearly visible. Macular subretinal hemorrhage and an RAM in the upper macula area were evident on FA and optical coherence tomography. After four intravitreal injections of ranibizumab, macular hemorrhage resolved, RAM disappeared, and visual acuity improved to 0.2. All cases were treated by intravitreal injection of anti-VEGF. After several injections, the macular hemorrhage or macular edema was resolved. RAM disappeared, and visual acuity improved. Conclusion: Intravitreal injection of anti-VEGF appears effective for age-related macular degeneration or diabetic macular edema with concomitant RAM. Although anti-VEGF intravitreal injections are not covered by health insurance for the treatment of RAM, their effectiveness means that the expansion of indications is desirable.

Successful Treatment of Hemi-Retinal Vein Occlusion with Macular Edema following Spinal Surgery Using Intravitreal Aflibercept and Retinal Photocoagulation: A Case Report.

Introduction: Perioperative visual loss (POVL) owing to hemi-retinal vein occlusion (HRVO) following prone positioning during spinal surgery is rare. Here, we report a case of HRVO with macular edema (ME) after spinal surgery that was successfully treated with intravitreal aflibercept (IVA) injections and retinal photocoagulation (RP). Case Presentation: A 63-year-old Japanese man underwent spinal surgery for lumbar spinal canal stenosis. Surgery was performed with the patient in the prone position under general anesthesia; the operation time was 305 min. No complications were associated with intraoperative anesthesia. On postoperative day 4, the patient noticed decreased visual acuity in his left eye and visited the Department of Ophthalmology on postoperative day 9. The best-corrected visual acuity (BCVA) in the left eye was 0.1. Fundus and optical coherence tomography revealed HRVO and ME in the left eye. IVA injections and RP were performed in the eye, which substantially decreased the ME and improved the patient's BCVA to 0.8. Conclusions: HRVO can cause POVL after prone positioning during spinal surgery. This is the first case of HRVO with ME after spinal surgery, which was successfully treated with IVA injections and RP.

A Case of Incidental and Uncomplicated Subretinal Triamcinolone Acetonide.

Introduction: Posterior subtenon injection of triamcinolone acetonide (PSTA) is commonly done to treat refractory cases of macular edema. Complications may arise from the procedure as well as from the use of the periocular steroid medications. Side effects include subconjunctival hemorrhage, progression of cataract, scleral perforation (resulting in subretinal, subhyaloid, or intravitreal injection of the drug), retinal detachment, ptosis, orbital fat prolapse, orbital abscess, infectious scleritis, ocular hypertension, and scleral abscess. Here we describe a case of inadvertent subretinal triamcinolone acetonide (TA) deposition from a PSTA procedure without any adverse vision-threatening outcomes. Case Presentation: We report a patient who presented with a history of superior temporal left eye macula-off rhegmatogenous retinal detachment, which was successfully repaired with a scleral buckle (SB), pars plana vitrectomy, and gas placement. Due to persistent diplopia, the SB was removed after 1 year post-operatively. Due to the development of cystoid macular edema, a PSTA was performed after the patient failed topical steroids and NSAIDs. The procedure was halted early due to unexpected resistance during the injection. A dilated fundus exam showed the presence of subretinal triamcinolone acetonide. The patient was observed and found to have no complications with almost complete resolution of the triamcinolone acetonide after 3 months. Conclusion: In previous SB patients, it is important to highlight the risk of globe penetration, subretinal deposition of TA, formation of retinal breaks, or reopening of prior retinal breaks with posterior subtenon injection, which could have adverse effects on the local retina as well as the risk of retinal detachment.

A case of accidental into-the-lens dexamethasone implant: watching or removing?

BACKGROUND: To report a case of cataract surgery in unintentional Ozurdex (Allergan, Inc., Irvine, California, USA) injection into the lens. CASE PRESENTATION: A 82-years old man reporting decreased visual acuity in his right eye came to our Ophthalmology service. Due to the clinical history, and on the basis of ophthalmoscopic and imaging examinations diabetic macular edema was diagnosed. Thus, intravitreal dexamethasone implant was scheduled and therefore performed. The following day Ozurdex appeared to be located into the lens. After careful evaluation and strict follow up examinations, due to the risks associated with the presence of the implant into the lens, phacoemulsification with Ozurdex removal and intraocular lens (IOL) implantation was scheduled and performed. CONCLUSIONS: In this case report we reported the surgical management of accidental into-the lens dexamethasone implant carefully taking into account the dexamethasone pharmacokinetic.

Topical and Subcutaneous Interferon-Alpha for the Treatment of Refractory Inflammatory Macular Edema.

PURPOSE: To evaluate the efficacy of topical interferon alpha-2b (tIFN a2b) and subcutaneous pegylated interferon alpha-2a (peg-IFN a2a) in the treatment of refractory pseudophakic (PME) and uveitic (UME) macular edema. METHODS: Retrospective case series of patients with PME or UME that was non-responsive to conventional therapies. Topical IFN a2b drops (1 MIU/ml) were commenced four times a day. Non-responders were offered treatment with subcutaneous peg-IFN a2a starting at 180 mcg weekly. RESULTS: Seven eyes of seven patients (three UME and four PME) were treated with tIFN a2b. Three eyes had complete ME resolution with tIFN treatment after a mean of 2.66 weeks (range 1-4 weeks) and no recurrence after a mean total course of 11.33 weeks (range 5-20 weeks). Two cases (both PME) had partial responses to tIFN treatment and two cases (both UME) failed to respond. Of the four eyes that incompletely responded to tIFN (treatment range 6 weeks to 4 months), three were treated with peg-IFN a2a, which invariably led to complete and sustained ME resolution. Adverse effects from topical treatment were mild and consisted mainly of superficial irritation. Adverse effects of subcutaneous treatment included nausea, vomiting, anorexia, and leukopenia, though none limited treatment. CONCLUSIONS: Topical IFNa-2b appears safe and effective in isolation or in conjunction with topical steroids for the treatment of inflammatory macular edema (IME) in about half of patients in our small series. All partial and non-responders had complete disease resolution with systemic IFN. Topical IFN a2b should be considered in patients with refractory IME.

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and consequently has enabled the introduction of new treatment methods. Moreover, artificial intelligence (AI) is likely to assist in selecting the best treatment option for patients in the near future. The aim of this comprehensive review is to re-evaluate the old but still relevant data on the RVO and confront them with new studies. The paper will provide a detailed overview of diagnosis, current treatment, prevention, and future therapeutic possibilities regarding RVO, as well as clarifying the mechanism of macular edema in this disease entity.

Timing of Switching to Steroid Implants in Cases of Recalcitrant Diabetic Macular Edema Not Responding to Anti-vascular Endothelial Growth Factor (VEGF) Therapy: A Real-World Study.

Purpose The purpose of this study is to examine the impact of the timing of the steroid switch on both visual and anatomical outcomes in diabetic macular edema (DME) eyes that have shown an inadequate response to multiple intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. In the treatment of DME, anti-VEGF injections are typically the initial course of action. However, in cases where DME persists despite anti-VEGF treatment, intravitreal dexamethasone implants (Ozurdex®, Allergan Inc., Irvine, CA) are often utilized. Despite this, there remains a lack of consensus regarding the optimal timing for transitioning to steroid treatment. This study aims to shed light on the potential benefits of adjusting the timing of the steroid switch in cases of recalcitrant DME.  Methods The eyes (n = 105) of 77 patients with recalcitrant DME were included in this retrospective, interventional, comparative study comprising three groups: participants switched to steroid implants after three anti-VEGF injections (Group I), four to six anti-VEGF injections (Group II), and more than six anti-VEGF injections (Group III). Anti-VEGF treatment failure was defined as a central retinal thickness (CRT) of ≥300 microns and/or a lack of visual improvement (≤1 line of visual gain according to Snellen acuity). The last follow-up took place after 10-12 weeks of Ozurdex® injections. Results Improvement was observed in 19 eyes (46%), 17 eyes (50%), and 10 eyes (33%) in Groups I, II, and III, respectively, after switching to dexamethasone implants. The best overall results (an improvement in vision and stabilization) were seen in Group II (32 eyes, 94%). The decrease in CRT was statistically significant in all three groups.  Conclusion Intravitreal dexamethasone implants improved functional and morphological outcomes in anti-VEGF-resistant DME eyes. After four to six anti-VEGF injections, switching to a steroid implant resulted in the best functional results.

Efficacy and Safety of Laser Therapy on Ischemic Central Retinal Vein Occlusion: A Systematic Review and Analysis of Clinical Studies.

Many studies have evaluated different treatments for ischemic central retinal vein occlusion (CRVO). Nevertheless, improvement and complication rates vary significantly. This systematic review aimed to evaluate the efficacy of laser therapy in treating ischemic CRVO compared with a control group using other treatments. The databases of PubMed, Google Scholar, and ClinicalTrials.gov were searched using a variety of keywords, including "ischemic central retinal vein occlusion," "CRVO," "laser," and "panretinal photocoagulation." After data extraction, each study's quality was assessed using the methodological index for nonrandomized studies (MINORS) or grading of recommendations, assessment, development, and evaluation or GRADE standards. A sum of 195 abstracts were reviewed, and seven clinical trials were eventually chosen. Of these, four were prospective studies, two were randomized controlled studies, and only one was a retrospective study. The assessment of potential biases in our included studies revealed that all these studies demonstrated moderate or high quality. Two studies were selected for meta-analysis, and the results showed no significant difference in visual acuity (VA) outcomes between the treated and the control groups (P = 0.17). In the remaining five studies, laser therapy was found to be more effective at neovascular complications, with a higher rate of neovascular glaucoma (NVG), iris neovascularization (NVI), neovascularisation at disc (NVD), and retinal neovascularization in the group without laser treatments. This review suggests that laser therapy is essential in preventing neovascular complications, such as NVG, NVI, NVD, and retinal neovascularization rather than improving VA. In addition, the combination of laser photocoagulation and intravitreal injection (IVI) improved VA, but further studies are required.

Anti-VEGF therapy for the long-term management of diabetic macular edema: a treat-to-target strategy based on macular morphology.

In an aging population, the prevalence and burden of diabetes mellitus, diabetic retinopathy, and vision-threatening diabetic macular edema (DME) are only expected to rise around the world. Similarly to other complications of diabetes mellitus, DME requires long-term management. This article aims to review the current challenges associated with the long-term management of DME, opportunities to improve outcomes for patients, and to develop a treat-to-target strategy based on macular morphology. At present, intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for the management of DME; however, best-achievable vision outcomes with treatment are reliant on frequent injections and close monitoring, which are difficult to maintain in current clinical practice because of the burden this imposes on patients. Achieving and maintaining good vision with treatment are the most important factors for patients with DME. Landmark trials have shown that vision gains with anti-VEGF therapy are typically accompanied by anatomical improvements (e.g., reductions in retinal thickness); therefore, multimodal imaging measures of macular morphology are often used in patients with DME to guide real-world treatment decisions. We would like to propose a hypothetical treat-to-target algorithm to guide physicians on treatment strategies for the long-term management of DME. Alternative measures of retinal fluid (e.g., persistence, stability, location) may be stronger predictors of visual acuity in DME, although further research is required to confirm whether alternate quantifiable biomarkers such as subretinal fluid and intraretinal fluid volumes can be used as a biomarker of clinical improvement. Identifying novel biomarkers and treatments that target neuroinflammation and neurodegeneration, improving patient-physician communication around treatment adherence, and using treat-to-target measures may help to ensure that the long-term benefits of treatment are realized.

The effect of intravitreal anti-VEGF injections on choroidal vascular index in patients with diabetic macular edema.

PURPOSE: This study aims to examine and compare the effects of intravitreal bevacizumab injection (IVB) at subfoveal 1500 micron (µm) and submacular 6000 µm in patients with diabetic macular edema (DME). METHODS: Fifty eyes of 45 patients with DME who completed six doses of IVB were included in the study group, and 50 eyes of 42 patients who had diabetic retinopathy (DR) but did not receive any treatment were included in the control group. Central macular thickness (CMT), central choroidal thickness (CCT), subfoveal and total choroidal area (TCA), and choroidal vascular index (CVI) were calculated and their changes at zero, three and six months were evaluated. RESULTS: At baseline, CVI was significantly lower in both the subfoveal and total macular areas in the study group (p = 0.004, p = 0.003). In the study group, a significant decrease was observed in CVI between zero and six months in the subfoveal area (p = 0.001). In the submacular area, the decrease in CVI in the study group was significant between zero to three months and zero to six months. There was moderate correlation between measurements of CVI in the subfoveal and total macular areas (r = 0.66, p < 0.001). CONCLUSION: These findings indicate that intravitreal bevacizumab injection reduces the CVI and the effects of intravitreal anti-VEGF on CVI emerge earlier and more prominently in the submacular 6000 µm area.

Role of inflammation in diabetic macular edema and neovascular age-related macular degeneration.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are multifactorial disorders that affect the macula and cause significant vision loss. Although inflammation and neoangiogenesis are hallmarks of DME and nAMD, respectively, they share some biochemical mediators. While inflammation is a trigger for the processes that lead to the development of DME, in nAMD inflammation seems to be the consequence of retinal pigment epithelium and Bruch membrane alterations. These pathophysiologic differences may be the key issue that justifies the difference in treatment strategies. Vascular endothelial growth factor inhibitors have changed the treatment of both diseases, however, many patients with DME fail to achieve the established therapeutic goals. From a clinical perspective, targeting inflammatory pathways with intravitreal corticosteroids has been proven to be effective in patients with DME. On the contrary, the clinical relevance of addressing inflammation in patients with nAMD has not been proven yet. We explore the role and implication of inflammation in the development of nAMD and DME and its therapeutical relevance.

A health economic pilot study comparing two diabetic retinopathy screening strategies.

To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.

Dipeptidyl peptidase 4 inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists do not worsen diabetic macular edema.

AIMS: There are limited studies on dipeptidyl-peptidase 4 inhibitor (DPP-4i), sodium glucose cotransporter 2 inhibitor (SGLT2-i), and glucagon-like peptide 1 (GLP-1) receptor agonist use and occurrence of diabetic macular edema (DME). The objective of this study was to determine the association between DPP-4i, SGLT2-i, and GLP-1 receptor agonist use and occurrence of DME. METHODS: Proportional hazard models were used to evaluate the change in hazard of developing DME associated with DPP-4i, SGLT2-i, or GLP-1 receptor agonist use. Models accounted for age at DR diagnosis, DR severity (proliferative vs non-proliferative stage), time-weighted average of HbA1c level, sex, and self-reported race/ethnicity. A p-value ≤ 0.05 was considered statistically significant. RESULTS: The hazard ratio of developing DME after diagnosis of DR was 1.2 (CI = 0.75 to 1.99; p = 0.43) for DPP-4i use, 0.93 (CI = 0.54 to 1.61; p = 0.81) for GLP-1 receptor agonist use, 0.82 (CI = 0.20 to 3.34; p = 0.78) for SGLT2-i use, 1.1 (CI = 0.75 to 1.59; p = 0.66) for any one medication use, 1.1 (CI = 0.62 to 2.09; p = 0.68) and for any two or more medications use. CONCLUSIONS: We did not find an association between DPP-4i, SGLT2-i, or GLP-1 receptor agonist use and increased hazard of development of DME among patients with DR.

Novel Approaches for Early Detection of Retinal Diseases Using Artificial Intelligence.

BACKGROUND: An increasing amount of people are globally affected by retinal diseases, such as diabetes, vascular occlusions, maculopathy, alterations of systemic circulation, and metabolic syndrome. AIM: This review will discuss novel technologies in and potential approaches to the detection and diagnosis of retinal diseases with the support of cutting-edge machines and artificial intelligence (AI). METHODS: The demand for retinal diagnostic imaging exams has increased, but the number of eye physicians or technicians is too little to meet the request. Thus, algorithms based on AI have been used, representing valid support for early detection and helping doctors to give diagnoses and make differential diagnosis. AI helps patients living far from hub centers to have tests and quick initial diagnosis, allowing them not to waste time in movements and waiting time for medical reply. RESULTS: Highly automated systems for screening, early diagnosis, grading and tailored therapy will facilitate the care of people, even in remote lands or countries. CONCLUSION: A potential massive and extensive use of AI might optimize the automated detection of tiny retinal alterations, allowing eye doctors to perform their best clinical assistance and to set the best options for the treatment of retinal diseases.