MYTHS AND TRUTHS OF THE ASSOCIATION OF RETINAL VASCULAR OCCLUSION WITH COVID-19.

PURPOSE: To critically review data published in the recent past to scrutinize a causal relationship between retinal vascular occlusion and COVID-19. METHOD: A comprehensive literature search was performed on Pubmed with the key words retinal vascular occlusion, retinal vein occlusion, retinal artery occlusion, and COVID-19. RESULTS: A total of 17 case reports were published during this period, and 10 were on retinal vein occlusion and 7 on retinal artery occlusion. Most of the published reports lacked convincing evidences in one or the other aspects, such as insufficient laboratory workup or presence of multiple confounding risk factors. CONCLUSION: In this index article, strength of the data is insufficient to establish a definitive cause-and-effect relationship of retinal vascular occlusive disorders with COVID-19. Hence, clinicians can continue to manage these cases according to the standard guidelines until there are more robust evidences to support this association to alter the diagnostic and treatment modalities.

Toxicity Threshold of Perfluorocarbon Liquids for Intraocular Use: Dose-Response Assessment of In Vitro Cytotoxicity of Possible Contaminants.

Purpose: This study assessed the cytotoxicity of the impurities detected in the perfluorooctane (PFO) batches for vitreoretinal surgery that were associated with serious adverse incidents of ocular toxicity, namely, the perfluorooctanoic acid (PFOA), 1H,1H,7H-dodecafluoro-1-heptanol (DFH), 1H-perfluorooctane (1H-PFO), ethylbenzene, anhydrous p-xylene, and perfluoro-2-butyltetrahydrofurane, and two additional substances 1H,1H,1H,2H,2H-perfluorooctane (5H-PFO) and hexafluoro-1,2,3,4-tetrachlorobutane. Methods: Serial dilutions were tested by in vitro direct contact cytotoxicity test, validated in accordance with the ISO 10993-5:2009 standard using BALB3T3 and ARPE-19 cell lines, after sample application for 24 hours. Results: Six of the eight tested substances were cytotoxic according to the above-mentioned ISO standard. Anhydrous p-xylene, ethylbenzene, and PFOA were the most cytotoxic impurities as traces 1.55 ppm, 1.06 ppm, and 28.4 ppm reached the cytotoxicity limit, respectively. Hexafluoro-1,2,3,4-tetrachlorobutane, DFH, and 1H-PFO were cytotoxic at 980, 22,500, and 123,000 ppm, respectively. Both 5H-PFO and perfluoro-2-butyltetrahydrofuran were non-cytotoxic at the highest available concentrations (≥970,000 ppm). The dose-response curves allowed to calculate the cytotoxic concentration (CC30) for each tested substance that would reduce 30% of cell viability and corresponding to the cytotoxicity threshold according to ISO 10993-5. Conclusions: Our study determined the in vitro cytotoxicity of several impurities in PFO associated with serious adverse incidents in retinal surgery patients. Translational Relevance: Severe cytotoxicity of some impurities previously found in toxic perfluorocarbon liquids was confirmed. The cytotoxicity test validated according to the ISO 10993-5:2009 standard is a sensible and fast method for reliable detection of the cytotoxicity in perfluorocarbon liquids to guarantee maximal safety for the patients.

The use of personal protective equipment in clinical ophthalmology during corona virus disease-2019: a review of international guidelines and literature.

PURPOSE OF REVIEW: The use of nonpharmaceutical interventions can prevent viral spread in COVID-19 pandemic and PPE forms a crucial part of this strategy. However, there are discrepancies in existing guidelines and a lack of consensus among ophthalmic communities. This review aims to identify general consensus and provides recommendation of PPE for most common ophthalmological scenarios. With a global shortage of PPE, extended use and reuse strategies are also discussed. RECENT FINDINGS: In this review, guidelines and resources were selected, based on a three-tier process. The first-tier resources were from international infection control organizations. The second-tier resources were from ophthalmological professional associations and colleges. The third-tier resources involved a PubMed search using the keywords 'COVID-19; coronavirus; personal protective equipment' performed on 1 May 2020. Non-English guidelines and literatures were excluded. SUMMARY: On the basis of our methodology, we included a total of 30 documents, including 5 resources from tier 1, 14 resources from tier 2 and 15 from tier 3. Different levels of protection are necessary. Whenever performing an aerosol generating procedure, maximum protection should be ensured, this includes FFP3 respirator, fluid resistant gown, goggles or face-shield and disposable gloves. Similar protection should be used for handling COVID-19-positive/suspected case but the use of FFP2 respirator is acceptable. During routine outpatient clinic in cases of negative triage, it is recommended to use ASTM III surgical mask, plastic apron, disposable gloves and eye protection with goggles or face-shield. Lastly, patients should be encouraged to wear surgical masks whenever possible.

New Brilliant Blue G Derivative as Pharmacological Tool in Retinal Surgery.

Our study was aimed at assessing the retinal binding of a new synthetic Brilliant Blue G (BBG) derivative (pure benzyl-Brilliant Blue G; PBB) ophthalmic formulation, to improve vitreoretinal surgery procedure. Protein affinity of the new molecule was evaluated in vitro (cell-free assay) and in silico. Furthermore, an ex vivo model of vitreoretinal surgery was developed by using porcine eyes to assess the pharmacological profile of PBB, compared to commercial formulations based on BBG and methyl-BBG (Me-BBG). PBB showed a higher affinity for proteins (p < 0.05), compared to BBG and Me-BBG. In vitro and in silico studies demonstrated that the high selectivity of PBB could be related to high lipophilicity and binding affinity to fibronectin, the main component of the retinal internal limiting membrane (ILM). The PBB staining capabilities were evaluated in porcine eyes in comparison with BBG and Me-BBG. Forty microliters of each formulation were slowly placed over the retinal surface and removed after 30 s. After that, ILM peeling was carried out, and the retina collected. BBG, Me-BBG, and PBB quantification in ILM and retina tissues was carried out by HPLC analysis. PBB levels in the ILM were significantly (p < 0.05) higher compared to BBG and Me-BBG formulations. On the contrary, PBB showed a much lower (p < 0.05) distribution in retina (52 ng/mg tissue) compared to BBG and Me-BBG, in particular PBB levels were significantly (p < 0.05) lower. Therefore, the new synthetic Brilliant Blue derivative (PBB) showed a great ILM selectivity in comparison to underneath retinal layers. In conclusion, these findings had high translational impact with a tangible improving in ex vivo model of retinal surgery, suggesting a future use during surgical practice.

Fluidics of Single and Double Blade Guillotine Vitrectomy Probes in Balanced Salt Solution and Artificial Vitreous.

PURPOSE: To assess the fluidics of double-vitreous cutter blade (DB) compared with single-blade (SB) guillotine with 23-, 25-, and 27-gauge vitrectomy probes. To assess flow characteristics and flow rates in viscous and viscoelastic fluids. METHODS: We used Particle Image Velocimetry to measure the flow field close to the tip of each cutter probe and we derived kinematic quantities of interest, such as kinetic energy and acceleration. We performed measurements both on a balanced salt solution (BSS) and on a viscoelastic artificial vitreous (AV). RESULTS: The flow rate is significantly higher with DB than SB vitrectomy probes, for a given pumping pressure and cutting rate. The fluid flow observed is very different between BSS and AV tests. CONCLUSIONS: The DB has more efficient fluidics than SB vitrectomy probe in all tested conditions. Fluid acceleration depends on the cutting frequency, especially in the case of measurements in AV. The flow rate strongly depends on the pressure and it is little affected by the cutting frequency, in a range of clinical interest. The 27-G DB produces flow rates similar to the 23- and 25-G SB, with significantly smaller acceleration. The flow induced in the AV is different from that in BSS and oscillates at different frequencies. TRANSLATIONAL RELEVANCE: DB cutters prove to be more efficient in terms of lower acceleration for a given flow rate. The latter is mainly controlled by aspiration pressure and less by cut rates. The influence of vitreous rheology deserves further investigations.

Controversies over the role of internal limiting membrane peeling during vitrectomy in macular hole surgery.

Surgical management of an idiopathic macular hole consists of vitrectomy to release vitreofoveal traction and intraocular tamponade to flatten and reappose the hole's edges. The intentional atraumatic removal of the internal limiting membrane has been proposed as cost-effective option in macular hole surgery. The internal limiting membrane contributes to tangential traction at the edges of the hole and acts as a platform on which glial cells proliferate. Removal of the internal limiting membrane increases the elasticity of the denuded macula and improves the anatomical success rate; however, the visual consequences of this surgical maneuver are still not fully known. We discuss the beneficial and adverse effects associated with internal limiting membrane peeling in macular hole surgery, highlighting the internal limiting membrane's role in macular hole etiology and pathogenesis and the anatomical and functional findings after its removal.

Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy.

BACKGROUND: The purpose of this study is to evaluate the role, the safety and the effectiveness of intravitreal bevacizumab (IVB) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy (PDR). DESIGN: Case-Control Study METHODS: Randomized controlled trial performed on 72 eyes of 68 patients affected by vitreous haemorrhage (VH) and tractional retinal detachment (TRD), which occurred as a consequence of active proliferative diabetic retinopathy (PDR). We randomly assigned eligible patients in a 1: 1: 1 ratio to receive a sham injection or an intravitreal injection of 1.25 mg of bevacizumab, either 7 or 20 days before the vitrectomy. In order to obtain three homogeneous groups of surgical complexity, we assigned to the following preoperative parameters a score from 0 to 3: a) vitreous haemorrhage, b) prior retinal laser-photocoagulation, c) morphological types of retinal detachment such as focal, hammock, central diffuse, table-top. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12, and 24 weeks after the surgery. MAIN OUTCOME MEASURES: Intraoperative management, safety, efficacy of IVB at different time injection as an adjunct to vitrectomy in the management of severe PDR RESULTS: Group A (sham injection): intraoperative bleeding occurred in 19 cases (79.1%), the use of endodiathermy was necessary in 13 patients (54.1%), relaxing retinotomy was performed on one patient (4.1%), and in four cases (16.6%) iatrogenic retinal breaks occurred. The surgical mean time was 84 minutes (SD 12 minutes). Group B (bevacizumab administered 7 days before vitrectomy): intraoperative bleeding occurred in two cases (8.3%) and the use of endodiathermy was necessary in two patients (8.3%). No iatrogenic breaks occurred during the surgery. The surgical mean time was 65 minutes (SD 18 minutes). Group C (bevacizumab administered 20 days before vitrectomy): intraoperative bleeding occurred in three cases (12.5%), the use of endodiathermy was necessary in three patients (1.5%), and an iatrogenic break occurred in one patient (4.1%) while the delamination of fibrovascular tissue was being performed. The surgical mean time was 69 minutes (SD 21 minutes). The average difference in the surgical time was statistically significant between group A and group B (p = 0.025), and between group A and group C (p = 0.031). At the end of the surgery, the retina was completely attached in all eyes. At the 6-month follow-up, we observed the development of tractional retinal detachment (TRD) in one out of 24 patients from group C (4%). CONCLUSIONS: A preoperative intravitreal injection of bevacizumab may represent a new strategy for the surgical treatment of severe PDR by reducing retinal and iris neovascularization: this would make surgery much easier and safer, thus improving the anatomical and functional prognosis. According to our study, the best surgical results are achieved performing the IVB 7 days preoperatively.