Macular Edema Research Articles

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression. Here, we interrogate the relationship between gut barrier dysfunction, endotoxaemia and systemic and intestinal neutrophilia in diabetic retinopathy. In a cohort of individuals with type 2 diabetes (n=58) with varying severity of diabetic retinopathy and DME, we characterised the abundance of circulating neutrophils by flow cytometry and markers of gut permeability and endotoxaemia by plasma ELISA. In a mouse model of type 2 diabetes, we examined the effects of diabetes on abundance and function of intestinal, blood and bone marrow neutrophils, gut barrier integrity, endotoxaemia and diabetic retinopathy severity. Pharmacological inhibition of NETosis was achieved by i.p. injection of the peptidyl arginine deiminase 4 inhibitor (PAD4i) GSK484 daily for 4 weeks between 6 and 7 months of type 2 diabetes. In human participants, neutrophilia was unique to individuals with type 2 diabetes with diabetic retinopathy and DME and was accompanied by heightened circulating markers of gut permeability. At late-stage diabetes, neutrophilia and gut barrier dysfunction were seen in db/db mice. The db/db mice exhibited an increase in stem-like pre-neutrophils in the intestine and bone marrow and a decrease in haematopoietic vascular reparative cells. In the db/db mouse intestine, enhanced loss of gut barrier integrity was associated with elevated intestinal NETosis. Inhibition of NETosis by the PAD4i GSK484 resulted in decreased abundance of premature neutrophils in the intestine and blood and resulted in neutrophil retention in the bone marrow compared with vehicle-treated db/db mice. Additionally, the PAD4i decreased senescence within the gut epithelium and yielded a slowing of diabetic retinopathy progression. Severity of diabetic retinopathy and DME were associated with peripheral neutrophilia, gut barrier dysfunction and endotoxaemia in the human participants. db/db mice exhibited intestinal neutrophilia, specifically stem-like pre-neutrophils, which was associated with elevated NETosis and decreased levels of vascular reparative cells. Chronic inhibition of NETosis in db/db mice reduced intestinal senescence and NETs in the retina. These changes were associated with reduced endotoxaemia and an anti-inflammatory bone marrow milieu with retention of pre-neutrophils in the bone marrow and increased gut infiltration of myeloid angiogenic cells. Collectively, PAD-4i treatment decreased gut barrier dysfunction, restoring physiological haematopoiesis and levels of haematopoietic vascular reparative cells.

Outcomes of ophthalmic nurse conducted phone call follow-up of cataract surgery patients at an Australian Public Hospital.

COVID-related clinic shutdowns mandated the use of a day 1 telephone follow-up the day after routine cataract surgery rather than clinic attendance. We investigated to see if this is a safe alternative to standard care. Ninety-nine patients who underwent a routine cataract extraction between 22 April 2020 and 19 August 2020 at our Hospital were included in this audit. On post-operative day 1, a standardised questionnaire which screened for ocular symptoms and the observance of correct post-operative procedure was administered. Additionally, an ophthalmic nurse delivered a set of instructions. Patients were then reviewed at our clinic on post-operative day 30. Complications and subsequent clinical management were recorded at this consultation. The complications found were largely in line with international data and included: prolonged anterior chamber inflammation, cystoid macular oedema, refractive surprise and phimosis. Management at 1-month patient review was in all cases expectant, and there were no complications requiring urgent attention. A nurse conducted telephone questionnaire on post-operative day 1 appears to be a safe alternative to traditional follow-up. With its implementation, ophthalmic nurses can help relieve strain on ophthalmology departments.

A novel two-stage and combined treatment of primary open-angle glaucoma and cataract: comparative efficacy and complications

Background. The approach to the treatment of patients with primary open-angle glaucoma and cataract is still a subject of debate, because when choosing a particular type of procedure, as well as determining the timing of its performance, it is necessary to consider a significant number of factors that may affect success of treatment. There are limited data on the outcomes of combined treatment of patients with primary open-angle glaucoma and complicated cataract, which includes phacoemulsification with intraocular lens (IOL) implantation and micropulse transscleral cyclophotocoagulation (MP-TSCPC). The purpose is to compare efficacy and to study the nature and frequency of complications when using novel, two-stage and combined surgical and laser methods for treating primary open-angle glaucoma with cataract. Materials and methods. The study includes 112 patients (112 eyes) with primary open-angle glaucoma stage I–IV and complicated cataract. There were 3 observation groups. In the first one (n = 34), phacoemulsification with IOL implantation was performed 1 month prior to MP-TSCPC. The second group (n = 36) included patients who underwent phacoemulsification with IOL implantation a month after MP-TSCPC. In the third group (n = 42), phacoemulsification with IOL implantation and MP-TSCPC were performed in one procedure. These groups did not statistically differ in terms of age, gender, baseline intraocular pressure, stage of primary open-angle glaucoma and nuclear lens density. The primary outcome measure was the normalization of intraocular pressure with or without the use of antiglaucoma medications and without need for repeated laser and incisional procedures after 1, 3 and 6 months. The secondary outcome measure was stabilization or expansion of visual fields 1, 3, and 6 months after treatment. The complication nature and rates were evaluated. Results. In the third group, where combined treatment was performed, the incidence of transient hypertension and inflammatory complications was statistically higher. There was a tendency to a higher incidence of corneal edema, cystoid macular edema, and hypotony as well; 7.1 % of patients required repeated MP-TSCPC, but this was statistically insignificant. According to the survival analysis, a statistically significant difference was found between the three groups in functional (p = 0.036) and hypotensive outcomes (p = 0.046), with the best result in the second group at 6 months of follow-up. Conclusions. The efficacy assessed by hypotensive and functional outcomes at a follow-up period of 6 months appeared to be statistically lower in the group of combined treatment compared to the groups in which two-stage treatment was conducted.

Features of the development of moderate diabetic macular edema in patients with type 2 diabetes in the short-term follow-up

Background. Diabetic macular edema (DME) is one of the main complications of diabetic retinopathy, which occurs in almost 12 % of patients and causes more than 10,000 new cases of blindness per year. About 5 % of patients with type 2 diabetes already have DME at the time of diagnosis. Thanks to the ra­pid development of research methods such as optical coherence tomography (OCT) and OCT-angiography, the possibilities of measuring retinal layer thickness, visualizing retinal and choroidal vessels have significantly expanded. The purpose of the study is to investigate the features of moderate diabetic macular edema (DME 2) in patients with type 2 diabetes. Materials and methods. Six hundred and eighty patients (1296 eyes) of the Ukrainian popu­lation with nonproliferative diabetic retinopathy and type 2 diabetes were under observation. In them, the nature and frequency of DME development were studied. Two hundred and three patients (360 eyes) with DME refused treatment, and eyes with DME 2 were selected from this group, and these patients were the target of our study. All of them were examined for uncorrected visual acuity, best corrected visual acuity, OCT and OCT-angiography indicators at presentation and after 3 months. Results. Moderate diabetic macular edema was detected in 56 eyes (15.56 %). Uncorrected visual acuity in these patients averaged 0.310 ± 0.004. Best corrected visual acuity was 0.4 ± 0.0 on average. According to OCT data, the average area thickness in quadrant 6 × 6 was 321.80 ± 1.40 μm, the minimum thickness of the retina in the fovea was 213.41 ± 2.30 μm, the average thickness of the retina in the central sector of the macula — 245.57 ± 2.50 μm, the average retinal volume in quadrant 6 × 6 — 9.23 ± 0.03 mm³, nerve fiber layer (NFL) + ganglion cell layer (GCL) + inner plexiform layer (IPL) average — 127.73 ± 0.10 μm, NFL + GCL + IPL min — 117.8 ± 0.1 μm, average thickness of GCL — 91.54 ± 0.20 μm, of NFL — 38.84 ± 0.10 μm. During OCT angiography, the surface area of the superficial foveal avascular zone (FAZ) was on average 0.51 ± 0.01 mm², the surface area of the deep FAZ was 0.59 ± 0.01 mm². The average density of the superficial capillary plexus was 47.75 ± 0.40 %. The average density of the deep capillary plexus was 48.52 ± 0.30 %. After 3 months, according to OCT, area thickness was 321.45 ± 1.34 μm, min in fovea — 213.41 ± 2.32 μm, central sector — 246.0 ± 2.4 μm, volume — 9.23 ± 0.03 mm³, NFL + GCL + IPL average — 127.52 ± 0.10 μm, NFL + GCL + IPL min — 117.59 ± 0.20 μm, GCL — 91.21 ± 0.20 μm, NFL — 38.84 ± 0.10 μm. According to OCT-angiography, superficial FAZ averaged 0.53 ± 0.01 mm², deep FAZ — 0.61 ± 0.01 mm². The ave­rage density of the superficial capillary plexus was 47.7 ± 0.4 %. The average density of the deep capillary plexus was 48.46 ± 0.40 %. Conclusions. The average frequency of DME 2 in patients with type 2 diabetes was 15.56 %. Uncorrected visual acuity appeared to have a statistically significant dependence on the area thickness (p < 0.01), min in fovea (p < 0.01), central sector (p < 0.01), NFL + GCL + IPL average (p < 0.01), NFL + GCL + IPL min (p < 0.01), GCL (p < 0.01), NFL (p < 0.05) according to OCT data, as well as on the average area of foveal avascular zone in the superficial and deep capillary plexus (p < 0.05), the density of the superficial and deep capillary plexus (p < 0.01) according to OCT angiography.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αVβ3/5/6 ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells. Binding of the anti-MFAP4 antibody, hAS0326, makes MFAP4 inaccessible for integrin receptor interaction and thereby hAS0326 blocked endothelial cell motility in vitro. Intravitreal hAS0326 inhibited retinal vascular lesion area and neovessel volume in a laser-induced choroidal neovascularization mouse model, vascular permeability in streptozotocin-induced retinopathy and vascular leakage area in a chronic non-human primate model of DL-2-aminoadipic acid-induced retinopathy. One dose of hAS0326 showed duration of efficacy of at least 12 weeks in the latter model. Moreover, hAS0326-treatment significantly enriched gene ontology terms involving reduction of integrin binding. Our data suggest that hAS0326 constitutes a promising treatment of neovascularization and vascular leakage in retinal diseases.

Efficacy of Ozurdex implants as second-line therapy for non-responders to anti-VEGF in retinal vein occlusion-associated macular edema: a retrospective cohort study.

Retinal vein occlusion (RVO) is a prevalent retinal vascular disorder characterized by retinal haemorrhage, neovascularization, and macular edema This study aimed to assess the structural and functional effects of intravitreal implant (Ozurdex) treatment as a second-line for RVO-associated macular edema in patients who did not respond to first-line anti-VEGF therapy. We conducted a retrospective observational cohort study using electronic health records of RVO patients at Salisbury District Hospital between January 2014 and December 2019. Inclusion criteria included patients diagnosed with central or branch RVO. Patients underwent ophthalmic evaluations at baseline, including central retinal thickness (CRT) and best-corrected visual acuity (BCVA) assessments. Statistical analysis was performed using IBM SPSS Statistics, employing various tests to determine significance. Sixteen eyes of 16 White British patients were evaluated. Most patients had branch RVO (52.95%), and 47.05% had central RVO. While anti-VEGF treatment significantly improved BCVA (p = 0.0061), Ozurdex did not result in additional gain (p = 0.747). Both treatments significantly reduced CRT (p = 0.0055 for anti-VEGF; p = 0.0079 for Ozurdex). No significant differences were observed between diabetic and non-diabetic BCVA patients receiving either treatment. Ozurdex emerges as a safe and effective option for persistent macular edema in RVO patients unresponsive to anti-VEGF therapy. Although structural improvements in CRT were observed following Ozurdex treatment, they did not correlate with additional gain in BCVA. Despite this, the reduced treatment frequency of Ozurdex compared to anti-VEGF injections may be advantageous, particularly for frail non-responding patients minimizing treatment burden.

Hyperglycemia-induced oxidative stress in the development of diabetic retinopathy

Diabetic retinopathy (DR), the leading cause of preventable blindness, is primarily caused by chronic hyperglycemia-induced oxidative stress. This review examines molecular mechanisms by which hyperglycemia-induced oxidative damage transmits into retinal tissue. We summarize the major pathways: polyol activation, advanced glycation end-products (AGEs), protein kinase C (PKC) dysregulation, and hexosamine pathway. Oxidative stress leads to mitochondrial dysfunction, apoptosis of retinal endothelium and pigment epithelium and activation of cytokines, as well as overexpression of vascular endothelial growth factor (VEGF). These processes together cause vascular leakage, macular edema and pathological angiogenesis. Trials of oxidative stress therapies (e.g. antioxidants, PKC inhibitors e.g., ruboxistaurin, and anti-VEGF agents e.g., ranibizumab, bevacizumab, aflibercept) as well as mitochondria targeted therapies are considered potential therapeutic approaches to improve DR prognosis. Further studies on DR pathophysiology and treatment are recommended to develop effective interventions for this vision threatening condition. Better prevention and management of DR requires early intervention and biomarker-based approaches.

Clinical features, diagnosis, management, and prognosis of circumscribed choroidal hemangioma.

Because of its benign nature and rarity, circumscribed choroidal hemangioma (CCH) often receives limited attention, leading to a high rate of misdiagnosis and a lack of standardized treatment protocols. We provide a thorough clarification of the demographics, clinical features, diagnosis, management, and prognosis of CCH. We conducted a systematic search of the PubMed, EMBASE, and Ovid databases up to December, 2023, to identify relevant studies. The study included 106 studies encompassing 3,854 patients with CCH. The demographic profile revealed a male preponderance (62%, 95% CI 61%-64%) and a peak incidence in the working-age population (30-50 years, 48%, 95% CI 39%-57%), with the right eye being involved in 50% of cases (95% CI 48%-53%). Clinically, the most common symptom was decreased vision (90%, 95% CI 78%-99%), followed by blurred vision, visual field defect, and metamorphopsia. Fundus examination frequently revealed an orange-colored tumor (80%, 95% CI 58%-96%) located subfoveally (48%, 95% CI 42%-53%), often accompanied by subretinal fluid (SRF) (84%, 95% CI 78%-89%) and sometimes exudative retinal detachment (69%, 95% CI 51%-85%). The proportion of correctly diagnosed CCH upon first presentation was 13% (95% CI 3%-26%), with CCH commonly misdiagnosed as unspecified choroidal tumors, choroidal metastasis, and central serous chorioretinopathy. Photodynamic therapy (PDT) was the most widely researched treatment, taking up 18% (95% CI 8%-31%), followed by observation, transpupillary thermotherapy (TTT), and laser photocoagulation. When no treatment was applied, 33% of patients experienced visual acuity improvement, which increased to 76% (95% CI 58%-90%) with radiotherapy and 58% (95% CI 50%-67%) with PDT. In terms of tumor shrinkage, radiotherapy was most effective (100%), with PDT close behind (95% CI 96%-100%), and TTT at 63% (95% CI 45%-80%). PDT led to SRF resolution in 89% (95% CI 77%-97%) of patients and cystoid macular edema (CME) resolution in 73% (95% CI 38%-97%), while radiotherapy achieved the highest efficacy with 100% SRF resolution (95% CI: 99%-100%) and 100% CME resolution (95% CI: 83%-100%). Complication rates were highest with radiotherapy (14%, 95% CI 5%-25%) and PDT (9%, 95% CI 4%-16%). First-line treatment failure rates were highest for TTT (71%, 95% CI 44%-92%) and laser (70%, 95% CI 28%-99%), with radiotherapy showing the lowest rate (0%, 95% CI 0%-2%). Recurrence rates were highest for laser (68%, 95% CI 17%-100%) and TTT (62%, 95% CI 26%-93%), whereas radiotherapy had the lowest recurrence rate (0%, 95% CI 0%-1%). CCH predominantly affects the working-age male population, often leading to vision impairment and SRF. The diagnosis of CCH remains challenging, with low accuracy and frequent misdiagnoses. While PDT is the most widely researched treatment, radiotherapy offers superior outcomes in visual acuity, tumor shrinkage, and resolution of SRF and CME, though it carries higher complication rates. This study highlights the need for improved diagnostic accuracy and a balanced approach to treatment.

A pharmacovigilance study on the safety of faricimab in real-world scenario using FDA adverse event reporting system database

ABSTRACT Background Faricimab is predominantly prescribed for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema related to retinal vein occlusion (RVO-ME). Currently, a notable absence of large-scale, real-world studies focusing on the adverse reactions of faricimab exists. Methods This study assesses the side effects of faricimab by analyzing reports of adverse events (AEs) from the FDA’s AE Reporting System (FAERS) database. Through disproportionality analysis, this study substantiates the drug’s safety oversight. Results Our study revealed 2,746 instances of adverse events linked to faricimab, spanning 21 system organ classes (SOCs). The study retained 121 significant disproportionality preferred terms (PTs) that met criteria across all four analytical methods. Faricimab-associated AEs not documented in the drug instructions included visual impairment, blindness, retinal hemorrhage, anterior chamber inflammation, keratic precipitates, dry eye, chorioretinitis, diabetic retinopathy, and others. Conclusion The majority of our results align with earlier clinical studies and the details outlined in the product’s manual. Additionally, we identified several unforeseen and potential AE signals related to faricimab use. These insights are instrumental for ongoing clinical surveillance and risk assessment associated with the drug.

Thrombolytic efficacy and safety of recombinant scu-PA in a rabbit retinal vein occlusion model.

Retinal vein occlusion (RVO) has become the second most common retinal vascular disease after diabetic retinopathy. Existing therapeutic approaches, including intravitreal injection of antivascular endothelial growth factors (anti-VEGFs) and/or glucocorticoids and laser therapy, primarily address secondary macular edema and neovascularisation. However, these strategies do not address the underlying cause of the disease and may have harmful side effects. There is an urgent need for therapies that have a better prognosis and include the administration of thrombolytics at an early stage. Therefore, in the present study, we investigated the thrombolytic effect of treatment with recombinant human Single-chain urokinase-type plasminogen activators (scu-PA)and the differences in its efficacy at different doses in a rabbit RVO model. In addition, through a series of ophthalmological examinations, such as optical coherence tomography (OCT) and electrophysiology, conducted to ascertain the effects of treatment with scu-PA on the ocular fibrinolytic system, we noted a definitive safety window for the vitreous administration of scu-PA. Therefore, this study is the first to confirm that an intravenous or vitreous cavity injection of scu-PA has definitive potential for treating RVO; however, additional clinical studies are needed for further validation.

Combination therapy of intravitreal ranibizumab and sub-tenon triamcinolone for treatment of resistant diabetic macular edema: a clinical study in Egypt

BackgroundAmong those aged 20–74 in industrialized countries, diabetic retinopathy (DR) is the main cause of visual impairment. Diabetic macular edema (DME) is the leading cause of blindness in people with DR. DME that is resistant to therapy is now being treated with a number of different management strategies. This research was to examine the efficacy of sub-tenon steroid and anti- vascular endothelial growth factor (VEGF) injections as a combination therapy for the treatment of resistant DME, owing to the synergistic effect of this combination.MethodsThis is a two-arm, randomized, prospective clinical trial that included 100 eyes of patients with refractory DME divided into 2 equal groups: group 1 received posterior subtenon triamcinolone (STTA) and anti-VEGF injections (0.5 mg ranibizumab), and group 2 received anti-VEGF injections (0.5 mg ranibizumab) only, in the same session. The 2 groups were followed up for a period of 6 months.ResultsGroup 1 showed significant improvements in best corrected visual acuity (BCVA) (from 0.20 ± 0.11 to 0.32 ± 0.12, p = 0.04) and central macular thickness (CMT) (from 393.2 ± 35.29 to 260.2 ± 11.43 µm, p = 0.001), with fewer injections required compared to Group 2. Recurrence rates were significantly higher in Group 2 (42% vs. 12%, p = 0.026). After injections, there was a noticeable rise in intraocular pressure (IOP) (16.02 ± 1.56 Vs 16.26 ± 1.24 in both groups respectively). However, this elevation is usually just transitory lasting for short periods of time and is within the safe, insignificant rise ranges.ConclusionThe use of combined therapy with anti-VEGF treatment and STTA has been found to be an effective and safe approach to managing resistant DME. The lower number of injections needed help to reduce the economic burden, especially under constrained financial circumstances.

An analysis of heavy silicone oil treatment for inferior proliferative vitreoretinopathy

PurposeProliferative vitreoretinopathy (PVR) is a complication of retinal detachment which requires multiple vitreoretinal surgical interventions and frequent use of oil endotamponade. In this study, we conducted an in-depth analysis of complications associated with the use of heavy silicone oil in the management of inferior PVR.MethodsA retrospective cohort study of 20 eyes that underwent vitrectomy for inferior PVR with use of heavy silicone oil (Densiron 68) between March 2021 and October 2022 at Oxford Eye Hospital. Complications were classified into major categories relating to intraocular pressure, inflammation, lens, and oil emulsification/migration. Visual outcomes and surgical success rate were also evaluated.ResultsFill-induced pressure spikes (> 30 mmHg) within 14 days post-surgery were common after Densiron tamponade, especially in patients previously on glaucoma drops. The number of glaucoma drugs were increased in 45% of patients during Densiron tamponade. In 20% of cases, an increased medication was continued long-term after Densiron removal. Significant cataract progression occurred in all phakic patients. In 25% of pseudophakic cases, posterior capsule opacification was noted. Inflammatory complications, such as anterior uveitis, were rare and any cystoid macular oedema was transient. No unexplained acute loss of vision following Densiron removal was encountered. The anatomical success rate at 30 days after Densiron removal was 70%. The mean (± SD) best-corrected visual acuities were 1.04 (± 0.79), 0.85 (± 0.62) and 0.50 (± 0.51) logMAR prior, during and after Densiron tamponade, respectively.ConclusionThe outcomes in this cohort treated with Densiron 68 were comparable to previously reported anatomical and functional results in cases with inferior PVR. IOP and lens-related complications require additional treatment during or after Densiron tamponade. Inflammatory complications rarely occurred over tamponade durations of around three months.Trial registrationAnalyses were conducted as an internal quality improvement audit and as such did not require external IRB review.

DOP018 Etrasimod for the treatment of Ulcerative Colitis: Up to 4 years of safety data from the global clinical programme

Abstract Background Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). The long-term safety, tolerability and efficacy of etrasimod are being evaluated in an ongoing open-label extension (OLE) study.1 We report an updated cumulative safety analysis from the etrasimod UC clinical programme with a maximum of 4 years of exposure. Methods Patients who received etrasimod in completed phase 2 (OASIS; OASIS OLE), phase 3 (ELEVATE UC 52; ELEVATE UC 12) and ongoing ELEVATE UC OLE (data cutoff 30 Aug 2023) and ES101002 OLE (data snapshot 30 Aug 2022) studies were included. Treatment-emergent adverse event (TEAE) frequency and exposure-adjusted incidence rates (IRs) per 1 patient-year (PY) were analysed. Results A total of 1196 patients received ≥1 dose of etrasimod 1 mg or 2 mg once daily with a mean (standard deviation) exposure of 70.66 (54.36) weeks, and 1619.5 PYs of total exposure. Demographics and baseline characteristics are reported in Table 1. Most TEAEs were nonserious and rarely led to discontinuation. The IRs of TEAEs of interest were generally low (Table 2). Serious infections and herpes zoster infections were infrequently reported (all IR ≤0.02). Three patients experienced four nonserious events of macular oedema (0.3%, IR <0.01), including one event leading to discontinuation that resolved. One patient experienced two nonserious events of cystoid macular oedema (<0.1%; IR <0.01) that resolved. Malignancies were uncommon and included five patients with serious events (0.4%), two patients with squamous cell carcinomas and one with basal cell carcinoma. Eleven patients (0.9%) had alanine aminotransferase (ALT) levels >3 times the upper limit of normal (ULN) at two consecutive post-baseline visits. Notably, no patients exhibited >3× ULN in either ALT or aspartate aminotransferase and >2× ULN in total bilirubin (laboratory criteria for Hy’s law). TEAEs leading to death were reported in three patients (all deemed unrelated to treatment). No serious adverse events of hypertension or bradycardia were reported. No events of second-degree Mobitz type 2 atrioventricular (AV) block or third-degree AV block occurred. Conclusion Etrasimod remains well tolerated in patients with moderately to severely active UC, with a favourable safety profile that has not changed with longer-term treatment exposure for up to 4 years.

Convolutional neural networks in diabetic eye disease detection: A survey on retinopathy and macular edema

Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME) are notable eye disorders affecting the retina’s inner side. This retina helps a person see and distinguish between colors, which is crucial for performing daily activities. It has been observed in long-term diabetic patients, and the count gradually increases. Manually identifying its presence can be time-consuming and may not yield accurate results, as it can lead to various stages that, if delayed, can cause visual Impairment. Emerging technologies and advancements in medical care have enabled automated mechanisms to perform this task. Machine learning (ML) and Deep learning (DL) are two emerging fields of Artificial Intelligence that help identify grading severity through retinal fundus images at early stages and properly treat patients. The paper reviews convolutional neural networks (CNN) with hybrid models of ML and DL algorithms to implement and achieve it, along with the assets, limitations, and gaps of each mechanism, and helps improve further research.

Safety and efficacy of a modified suprachoroidal silicone tube shunt implant in primary open angle and pseudo-exfoliative glaucoma.

To assess the safety and efficacy of a modified suprachoroidal silicone tube (SST) shunt in patients with primary open-angle glaucoma (POAG) and pseudo-exfoliative glaucoma (PXG) in this experimental study. In this single-center, retrospective longitudinal data analysis 66 eyes of 59 patients having POAG and PXG were included and treated with modified SST shunt in combination with cataract or as a stand-alone procedure. Pre- and postoperative intraocular pressure (IOP), best corrected visual acuity (BCVA), C/D ratio and ocular adverse events (AEs) were assessed in all participants. The average follow-up period was 18.56 ± 7.93 months. Mean baseline IOP reduced from 27.02 ± 5.43 mmHg to 13.23 ± 3.70 mmHg (p < 0.001). Mean number of ocular hypotensive medications reduced from 3.17 ± 0.89 to 1.83 ± 1.44 (p < 0.001). BCVA remained stable in 49 eyes (74.2%) throughout the follow-up period. Mean baseline BCVA of 0.73 ± 0.27 slightly declined to 0.68 ± 0.30 at the final follow-up (p < 0.001). Three adverse events of special interest (AESI) were observed hypotonic maculopathy, anterior chamber inflammation with pupillary membranes, and macular edema. None of these events was related to the SST shunt. Other complications such as intra and early postoperative hyphema in 3 and tube-iris contact causing slight corectopia in 2 cases were noted. The surgical technique and device studied in this work demonstrated a good safety profile and signal of efficacy. This device may serve as a bridge between minimally invasive glaucoma surgeries (MIGS) and conventional filtering or episcleral tube shunt surgeries. A larger scale prospective trial is planned.

Effect of intravitreal Bevacizumab on coagulation profile of patients with diabetic retinopathy

Objectives: Intravitreal injections of Bevacizumab are widely used all over the world to treat Diabetic Retinopathy. However, there are thromboembolic events reported with its use. As blood coagulation is related with thromboembolism, the purpose of this study was to determine the effect of intravitreal injection of Bevacizumab on the coagulation profile of diabetic patients. Methods: It was a quasi-experimental study, conducted at Department of Ophthalmology, Lahore General Hospital from January 2023 to August 2023. Patients with treatment naïve proliferative DR and diabetic macular edema were included and those with renal disease, hypertensive retinopathy, chronic liver disease, ischemic heart disease, previous history of stroke, retinal vascular occlusion, any malignancy, history of using anti coagulants and aspirin and the patients who lost to follow up and did not complete the blood work up after injection were excluded. Patients’ Prothrombin time, bleeding time, clotting time, international normalized ratio and activated partial thromboplastin time were checked before and one week after intravitreal injection of Bevacizumab. Paired t test was used for analysis and p &lt; 0.05 was set for significance. Results: There were 138 patients who fulfilled the inclusion criteria (92 males and 46 females). The mean age was 55±8 years. There was statistically insignificant difference between the coagulation profile before and after intravitreal injection of Bevacizumab. Conclusion: Coagulation profile is not affected after one intravitreal injection of Bevacizumab. Other factors must be taken into account while injecting Bevacizumab in patients with history of thromboembolic events. doi: https://doi.org/10.12669/pjms.41.2.10289 How to cite this: Khalid I, Malik TG, Tariq H, Sajid U. Effect of intravitreal Bevacizumab on coagulation profile of patients with diabetic retinopathy. Pak J Med Sci. 2025;41(2):355-358. doi: https://doi.org/10.12669/pjms.41.2.10289 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nd:YAG Laser Iridotomy Versus Surgical Iridectomy in Descemet Membrane Endothelial Keratoplasty: Comparison of Postoperative Outcome and Incidence of Ocular Hypertension.

To evaluate outcome and incidence of ocular hypertension after Descemet membrane endothelial keratoplasty (DMEK) and DMEK combined with cataract surgery (triple DMEK) after Nd:YAG laser iridotomy (IO) and surgical iridectomy (IE). This is a single-center, retrospective cohort study of patients who underwent DMEK or triple DMEK surgery at the Department of Ophthalmology, University Hospital Düsseldorf, Germany, from January 2018 to June 2020 and had received either a prophylactic preoperative IO or an intraoperative IE. Patient demographic data; best corrected visual acuity; central corneal thickness; intraocular pressure (IOP); endothelial cell density; and complications such as occurrence of early postoperative IOP elevation, macular edema, rebubbling rate, and incidence of glaucoma were analyzed. A total of 75 patients were included in each study arm with a follow-up of 22.04 ± 12.8 months. Best corrected visual acuity significantly increased postoperatively in both cohorts without significant differences. Early postoperative IOP elevation due to pupillary block was significantly more common in eyes with IO (33.3%, n = 25) than with IE (2.67%, n = 2, P < 0.001). The incidence of de novo glaucoma was 5.34% in both cohorts without significant differences in prevalence at the last follow-up (YAG IO cohort: 17.3%, IE cohort: 14.7%, P > 0.05). Rebubbling was required in 16% (n = 12) of eyes in each cohort (P > 0.999). Postoperative pupillary block after DMEK occurs significantly more often after preoperative Nd:YAG laser iridotomy compared with surgical intraoperative iridectomy but does not negatively affect long-term visual outcome or glaucoma incidence after DMEK.

Noncryopexy versus cryopexy treatment during scleral buckling: a systematic review and meta-analysis.

To evaluate the differences in surgical outcomes between scleral buckling (SB) with noncryopexy and cryopexy methods. We systematically searched the Embase, Medline, Cochrane Library, and Scopus databases for randomized controlled trials (RCTs) published from their inception until January 1, 2024. A random-effects model was applied, and outcomes are presented as risk ratios (RRs) or standardized mean differences with 95% confidence intervals (CIs). The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria. We included seven RCTs involving a total of 1103 patients. The meta-analysis revealed comparable retinal reattachment rates between noncryopexy and cryopexy methods (RR: 1.00; 95% CI: 0.96-1.05). Our subgroup analysis revealed similar results between nonretinopexy and laser retinopexy subgroups. Moreover, postoperative visual acuity (VA) and complication rates were comparable between noncryopexy and cryopexy methods (proportion of eyes with postoperative VA of 20/40 or better: RR: 1.24, 95% CI: 0.83-1.85; macular pucker: RR: 1.08, 95% CI: 0.53-2.21; cystoid macular oedema: RR: 1.01, 95% CI: 0.79-1.30; and subretinal pigmentary migration: RR: 0.34, 95% CI: 0.08-1.38). However, the certainty of evidence for these outcomes was low to very low, indicating the need for cautious interpretation of these findings. Similar surgical outcomes were noted between noncryopexy and cryopexy methods in SB, suggesting that both methods are effective in repairing rhegmatogenous retinal detachment. However, future studies on a larger scale and with longer follow-ups may be necessary to detect late redetachment and complications.

Anatomical and functional changes after internal limiting membrane peeling.

Internal limiting membrane (ILM) peeling has been an acceptable step in vitrectomy surgeries for various retinal diseases such as macular hole, chronic macular edema following epiretinal membrane (ERM), and vitreoretinal traction. Despite all the benefits, this procedure has some side effects, which may lead to structural damage and functional vision loss. Light and dye toxicity may induce reversible and irreversible retina damage, which will be observed in postoperative optical coherence tomography scans. Retinal nerve fiber layer damage is attributed to ganglion cell degeneration and axonal transport alteration, and dissociated optic nerve fiber layer is due to Müller cell damage. Eccentric MHs and recurrence of previous MHs may also lead to vision loss. Iatrogenic retinal damage may cause structural retinal changes without significant vision loss or progression to choroidal neovascularization. The mechanism of persistent macular edema after membrane peeling is still unclear, but it has been related to tractional trauma and blood-retina barrier damage. The reappearance of ERM is another cause of decreased vision after ILM peeling, which might be secondary to incomplete membrane removal. In glaucoma patients, ILM peeling is associated with significantly worsening the mean deviation on the visual field test after the surgery. We discussed various causes of vision loss and structural changes following ILM peeling. These causes may be attributed to the surgical procedure itself or the associated steps, instruments, and dyes used during the ILM peeling procedure.

Recent trends and outcomes in immediate and delayed sequential bilateral cataract surgeries: a nationwide cohort study in South Korea.

To analyze the latest annual trends in immediate sequential bilateral cataract surgery (ISBCS) and delayed sequential bilateral cataract surgery (DSBCS) among patients with bilateral cataracts in Korea, and to identify the factors influencing the choice of surgery and the outcomes associated with ISBCS and DSBCS. This retrospective, nationwide cohort study included all patients aged 65 and older who were covered by the Korean National Health Insurance and underwent ISBCS or DSBCS from 2016 to 2021. The study recorded yearly numbers of ISBCS and DSBCS procedures, the interval between surgeries in DSBCS cases, patient demographics, types of implanted intraocular lenses (IOLs), and the incidence of cystoid macular edema and endophthalmitis following ISBCS or DSBCS. A total of 50 878 (7.2%) patients underwent ISBCS, and 658 609 (92.8%) patients underwent DSBCS. ISBCS cases more than doubled in 2020 (7902) from 2019 (3703) before increasing even more significantly in number in 2021 (33 645). Age, hospital size, ocular and systemic comorbidities, type of IOL, and calendar year were associated with receiving ISBCS. In 2020 alone, the incidence of postoperative endophthalmitis among ISBCS patients was significantly higher (1.39 per 1000 procedures) than among DSBCS patients (0.40 per 1000 procedures; P = 0.001). The number of patients undergoing ISBCS for bilateral cataracts increased annually, particularly after the onset of the COVID-19 pandemic in Korea in 2020. However, this significant rise in ISBCS also led to a surge in the incidence of postoperative endophthalmitis in 2020.