Efficacy of ranibizumab and aflibercept on reducing maximum diameter of largest cyst in diabetic cystoid macular edema: MARMASIA study group.

PURPOSE: This study aimed to compare the effect of intravitreal aflibercept (IVA) and ranibizumab (IVR) on the maximal diameter of the largest intraretinal cyst (mdIRC), indicating chronicity in patients with diabetic cystoid macular edema (CME). METHODS: This retrospective, comparative study included a subgroup of patients from the MARMASIA Study with treatment-naïve diabetic CME who had IVA (IVA group) or IVR (IVR group) on a pro re nata regimen after a loading dose of 3-monthly injections and followed-up for 24 months. Best-corrected visual acuity (logMAR), central macular thickness (CMT, µm), and mdIRC (µm) and their changes during the study period in the IVA and IVR groups were compared. RESULTS: A total of 175 eyes (65 [37.1%] in IVA and 110 [62.9%] in IVR group) of 113 patients were included in the study analysis. Both groups had statistically significant improvements in BCVA and CMT during the follow-up (p < 0.05 for all), which were comparable between the groups at each time point. However, the mean reduction in mdIRCs was consistently and significantly higher in the IVA group compared to the IVR group at each follow-up examination (F[1, 3.52] = 6.93, p = 0.009). CONCLUSION: IVA seems to have a greater impact in reducing cyst sizes than IVR in diabetic CME.

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.

Real-World Outcomes of Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema in Türkiye: MARMASIA Study Group Report No. 1.

Objectives: This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye. Materials and Methods: This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients' baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, µm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated. Results: The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 µm. The mean changes from baseline in BCVA were +7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 µm at the 3, 6, 12, 24, and 36-month visits (p<0.001 for all). The median cumulative number of anti-VEGF IVI was 3.0, 3.0, 5.0, 7.0, and 9.0, respectively. The overall anti-VEGF switch and IDI combination rates were 18.5% (253/1372 eyes) and 35.0% (480/1372 eyes), respectively. Conclusion: This largest real-life study of DME from Türkiye demonstrated BCVA gains inferior to randomized controlled trials, mainly due to the lower number of IVI. However, with the lower baseline BCVA and higher IDI combination rates in our cohorts, these gains were relatively superior to other real-life study counterparts.

Expression of key SARS-CoV-2 entry molecules in surgically obtained human retinal biopsies.

PURPOSE: To investigate the presence of ACE2, TMPRSS2 and Furin, i.e., a key player in the ocular infection with SARS-COV-2, in surgically obtained human retinal tissue samples from SARS-CoV-2-negative patients, using gene expression analysis. METHODS: The mechanisms and entry paths of ocular infections have been ill-defined so far. To better understand the possible entry routes, we used surgically explanted retinal tissue from nine patients that were not infected with SARS-CoV-2 and analyzed the message expression of the three key molecules that confer viral entry into cells using polymerase chain reaction. RESULTS: The median age of the patients (n = 9) included in the study was 52 years (IQR 48, 55). Eight patients underwent surgery for rhegmatogenous retinal detachment and one patient for tractional retinal detachment. Gene expression for the proteins studied was detected in all nine patients. The results of analysis by Livak's method (2001) demonstrated a median TMPRSS2 gene expression value of 20.9 (IQR 11.7, 33.7), a median ACE2 gene expression value of 2.09 (IQR 1.14, 2.79) and a median Furin gene expression value of 8.33 (IQR 5.90, 11.8). CONCLUSION: In conclusion, TMPRSS2, Furin and ACE2 are expressed in the retina and may contribute to the retinal involvement in COVID-19 patients. Expression may vary among individuals, which may explain why some patients may be more prone to retinal involvement during SARS-CoV-2 infection COVID-19 patients than others. Variability in the expression of TMPRSS2, Furin and ACE2 proteins themselves may also explain the presence or development of retinal symptoms of varying severity.

Current Approaches in Treatment of Diabetic Retinopathy and Future Perspectives.

Diabetes mellitus (DM) is a metabolic disease, which is the most common cause of low vision in developing countries and affects almost all systems of the body. In view of the increase in DM prevalence in the world, it would not be a surprise that diabetic retinopathy (DR) and other vascular complications related to diabetes become a serious public health problem. Currently, vascular endothelial growth factor, laser photocoagulation, and intravitreal steroids are the mainstays for DR treatment, but the efficacy of these treatment strategies remains insufficient. Therefore, new treatment modalities for DR have been developed, such as stem cell therapies, extracellular vesicular system, and nanodrug delivery systems. Although there have been several reviews in the literature on the treatment of DR, we have not confronted any review that has the titles of all these topics. With this review, we aim to present the pathophysiology of DR and to review the current and promising new treatment methods based on stem cells, extracellular vesicular system, and nanodrug delivery systems for the future of DR management.

Linear mixed model better than repeated measures analysis.

We have some criticism regarding some technical issues. Mixed models have begun to play a pivotal role in statistical analyses and offer many advantages over more conventional analyses regarding repeated variance analyses. First, they allow to avoid conducting multiple t-tests; second, they can accommodate for within-patient correlation; third, they allow to incorporate not only a random coefficient, but also a random slope, typically 'linear' time in longitudinal case series when there are enough data and patients' trajectories vary a lot and improving model fit.

Characteristics of pediatric and adult cases with open globe injury and factors affecting visual outcomes: A retrospective analysis of 294 cases from Turkey.

BACKGROUND: This study aimed to evaluate 1-year follow-up results of cases that were diagnosed with open globe injury (OGI), to compare trauma-related characteristics between pediatric and adult cases, and to determine risk factors for a poor final visual acuity. METHODS: This study enrolled 294 cases that met the OGI definition and were followed up for at least 1 year. Demographic and clinical features regarding ocular trauma were recorded. The cases were divided into two groups according to age: pediatric (≤16 years) and adult (>16 years) groups. RESULTS: Children were exposed to accidents that led to OGI mostly at home, whereas adults were exposed to such accidents mostly in the office. Penetrating injuries were more common in children than in adults, and injuries most commonly occurred owing to spiky objects. Zone I injuries were most frequent in both children and adults. The frequency of high-grade injuries increased with age. Foreign body injuries and multiple surgeries were more common in adults than in children. There was no difference between the two age groups based on ocular trauma score (OTS) and visual acuity. OTS predicted the need for multiple surgeries. In the adult group, age, multiple surgeries, and initial visual acuity were significant risk factors for the final visual acuity that was achieved. CONCLUSION: OGI causes and risk factors for poor final visual outcomes differ in adults and children. The knowledge of these differences is crucial for taking adequate preventive measures and decreasing morbidity.