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.

Is serum vitamin D associated with diabetic retinopathy and its severity or with diabetes itself ?

CLINICAL RELEVANCE: Vitamin D (VitD) deficiency, which is found in approximately one-third of the population of the world, may play a role in the pathogenesis of diabetic retinopathy. Physicians following diabetes patients should be aware of this relationship and should refer patients to for ophthalmic care for control in a timely manner. BACKGROUND: Diabetic retinopathy is one of the most common complications of diabetic microvascular disease. VitD deficiency has been implicated in the pathogenesis and progression of diabetes and may have a role in development and severity of diabetic retinopathy. The aim of this study was to examine the relationship of serum VitD and some laboratory parameters with the presence of diabetes and retinopathy. METHODS: In this study, which has a retrospective epidemiological study design, comprehensive ophthalmologic examination data from the eye clinic, laboratory data from fasting blood tests, and internal medicine outpatient clinic examination data were reviewed. All participants were divided into four groups: 109 healthy controls, and 165 patients with type 2 diabetes of whom 54 did not have retinopathy, 64 had proliferative diabetic retinopathy, and 47 had non-proliferative diabetic retinopathy. Participants were also divided into four groups according to their serum VitD levels. Serum 25(OH)D, HbA1C, creatine, calcium, phosphate, triglyceride, low-density lipoprotein, and high-density lipoprotein levels were evaluated. RESULTS: In the whole study cohort, 152 (55.5%) were female and 122 (44.5%) were male. A statistically significant difference was observed in VitD between the healthy group and the diabetic and proliferative diabetic retinopathy groups (p ≤ 0.001). However, no significant correlation was observed between the presence of diabetes and retinopathy and serum VitD in logistic regression analyses (p > 0.05). CONCLUSION: Diabetic patients have lower 25(OH)D than non-diabetic patients and there is no direct relationship between 25(OH)D and the development of diabetic retinopathy.

Survey of Intravitreal Injection Preferences for the Treatment of Age-Related Macular Degeneration and Macular Edema Among Members of the Turkish Ophthalmological Association.

Objectives: To analyze the current preferences of ophthalmologists for the treatment of macular edema and age-related macular degeneration (AMD) and to evaluate off-label use of bevacizumab in Turkey. Materials and Methods: All members of the Turkish Ophthalmological Association were contacted by e-mail to complete an anonymous, 47-question internet-based survey. The second part of the survey (questions 36-47) was evaluated. Results: When current legal regulations were considered, ophthalmologists used bevacizumab as the first-line agent in patients with diabetic macular edema (DME), AMD, and retinal vein occlusion (RVO) (58.25%, 55.89%, and 52.29%, respectively). When economic and legal constraints were disregarded, the participants' preference for bevacizumab in the treatment of DME, AMD, and RVO decreased (11.64%, 10.58%, and 10.93%, respectively). Approximately three-quarters (75.75%) of ophthalmologists stated that dispensing multiple syringes from a single bevacizumab bottle could increase the risk of endophthalmitis. Most participants (93.68%) did not feel legally safe from harm caused by off-label bevacizumab use. However, 66.43% of ophthalmologists stated that bevacizumab is as effective as other anti-vascular endothelial growth factor (anti-VEGF) drugs. Conclusion: Bevacizumab is widely used as a first-line treatment for all indications of anti-VEGF use in the current reimbursement conditions, which preclude the right of ophthalmologists to treat according to their own preferences.

Survey of Intravitreal Injection Techniques and Treatment Protocols Among Members of the Turkish Ophthalmological Association.

OBJECTIVES: To describe the intravitreal injection (IVI) techniques, practices, and treatment protocols of ophthalmologists in Turkey from May 20, 2020 to June 4, 2020. MATERIALS AND METHODS: All members of the Turkish Ophthalmological Association were contacted by e-mail to complete an anonymous, 47-question internet-based survey. RESULTS: Thirteen percent of the participants prescribed prophylactic antibiotics pre-injection, 63.8% (406/636) used antibiotic drops immediately after injection, and 91.8% prescribed topical antibiotics. The majority of IVI procedures were performed in an operating room (65.3%) or clean room (33.6%). Most surgeons used sterile gloves, masks, sterile drape, sterile fenestrated cover, and sterile eyelid speculum. Multispecialists (M) preferred to wear sterile gloves more than retina specialists (RS) (99.0% vs. 95.3%; p=0.004). Also, M prescribed antibiotics more than RS (93.7% vs. 88.8%; p=0.029). RS dilated the pupil more frequently than M (48.3% vs. 39.0%) (p=0.020). RS were more familiar to use different quadrants (right p=0.012; left p=0.001). Most surgeons (82.8%) did not perform injections in both eyes on the same day. CONCLUSION: Ophthalmologists in Turkey employ a wide range of techniques in care before, during, and after IVI. In addition, IVI techniques and treatment protocols differed between RS and M. Further research is needed to elucidate best practice patterns.

Bilateral Sequential Paracentral Acute Middle Maculopathy.

We aim to present a case with bilateral sequential paracentral acute middle maculopathy (PAMM). A 57-year-old man presented with paracentral scotoma in the left eye. The patient's multimodal imaging findings were consistent with PAMM in the left eye. Extensive systemic work-up revealed hypertension and a history of cerebrovascular event. One year after initial presentation, the patient had a subsequent decrease in visual acuity in the right eye and developed optical coherence tomography findings consistent with PAMM, whereas the left eye showed resolved PAMM findings. Although rare, PAMM can occur bilaterally. Clinicians should monitor unilateral PAMM patients with systemic vasculopathy for involvement in the fellow eye.