Anatomic-Functional Correlates in Lesions of Retinal Vein Occlusion.

Purpose: To evaluate anatomic-functional associations at sites of retinal lesions in retinal vein occlusion (RVO). Methods: This pilot, prospective, observational study was conducted at the Northern Ireland Clinical Research Facility (NICRF) of Queen's University and the Belfast Health and Social Care Trust, Northern Ireland, between August 1, 2018, and September 30, 2019. The study included 10 treatment-naïve patients with RVO (10 RVO eyes and 10 fellow eyes). There were 81 points/sites assessed for each eye at baseline; six patients were re-assessed 6 months after anti-vascular endothelial growth factor therapy at the same locations. We investigated associations between retinal sensitivity and presence of structural RVO lesions, including retinal ischemia, hemorrhages, intraretinal fluid (IRF) and subretinal fluid outside the foveal/parafoveal regions. Comparisons were made between RVO eyes and fellow eyes at baseline, and between RVO eyes at baseline and at 6 months after treatment. Regression models were used to investigate anatomic-functional associations. Results: At baseline, strong associations were found between reduced retinal sensitivity and presence of ischemia (estimate = -2.08 dB; P < 0.001), intraretinal fluid (estimate = -7.82 dB; P < 0.001), and subretinal fluid (estimate = -8.66 dB; P < 0.001). Resolution of subretinal fluid but not intraretinal fluid was associated with improved function (estimate = 2.40 dB [P = 0.022]; estimate = 1.16 dB [P = 0.228], respectively). However, reperfusion of ischemic retina, observed in 31 of 486 points (6%) 6 months after anti-vascular endothelial growth factor therapy, was associated with a further decrease in retinal sensitivity (estimate = -2.34 dB; P = 0.035). Conclusions: Retinal sensitivity was decreased at sites of RVO lesions. Decreased function at sites of retinal ischemia did not recover after treatment, even when reperfusion occurred.

IMPACT OF RETINAL ISCHEMIA ON FUNCTIONAL AND ANATOMICAL OUTCOMES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN PATIENTS WITH RETINAL VEIN OCCLUSION.

PURPOSE: To compare the impact of the classification of retinal vein occlusion (RVO) into ischemic or nonischemic forms on outcomes after anti-vascular endothelial growth factor therapy. METHODS: Retrospective review of consecutive patients with RVO evaluated at the Belfast Health and Social Care Trust between July 1, 2014, and December 31, 2015. Outcomes, including gain of ≥10 and ≥15 letters at 12 months, mean change in best-corrected visual acuity from baseline to 12 months, resolution of macular edema at 12 months, and development of neovascular complications and epiretinal membrane after anti-vascular endothelial growth factor therapy, were compared between ischemic and nonischemic eyes using regression models. RESULTS: One hundred and seventeen eyes (115 patients), 58 with central RVO and 59 with branch RVO, were included. A greater proportion of eyes with ischemic branch RVO gained ≥10 and ≥15 letters at 12 months than those with nonischemic branch RVO (P = 0.005 and P = 0.016, respectively). No statistically significant differences in visual outcomes were observed between ischemic and nonischemic central RVO. Retinal vein occlusion classification was not associated with anatomical outcomes after treatment. CONCLUSION: Findings support the use of anti-vascular endothelial growth factors in ischemic and nonischemic forms of RVO.

Ischemic retinal vein occlusion: characterizing the more severe spectrum of retinal vein occlusion.

Retinal vein occlusion (RVO)-including central RVO, branch RVO, and hemicentral and hemispheric RVO-is the second most common vascular cause of visual loss, surpassed only by diabetic retinopathy. The presence and extent of retinal ischemia in RVO is associated with a worse prognosis. On this basis, most previously conducted studies considered ischemic retinal vein occlusion (iRVO) and non-iRVO as separate entities based on set thresholds of existing retinal ischemia as determined by fundus fluorescein angiography. Other diagnostic technologies have been used specifically in the differentiation of ischemic central retinal vein occlusion and nonischemic central retinal vein occlusion. To date, there is no fully accepted definition for iRVO. Some clinicians and researchers may favor establishing a clear differentiation between these forms of RVO; others may prefer not to consider iRVO as a separate entity. Whatever the case, retinal ischemia in RVO confers a higher risk of visual loss and neovascular complications; thus, it should be determined as accurately as possible in patients with this disease and be considered in clinical and experimental studies. Most recently conducted clinical trials evaluating new treatments for macular edema secondary to RVO included none or only few patients with iRVO based on previous definitions (i.e., few patients with sizeable areas of retinal ischemia were recruited in these trials), and thus it is unclear whether the results observed in recruited patients could be extrapolated to those with retinal ischemia. There has been scant research aiming at developing and/or testing treatments for retinal ischemia, as well as to prevent new vessel formation as a result of RVO. We provide a detailed review of the knowledge gathered over the years on iRVO, from controversies on its definition and diagnosis to the understanding of its epidemiology, risk factors and pathogenesis, the structural and functional effects of this disease in the eye and its complications, natural history, and outcomes after treatment. In each section, the definition of iRVO used is given so, independently of whether iRVO is considered a separate clinical entity or a more severe end of the spectrum of RVO, the information will be useful to clinicians to determine patient's risk, guide therapeutic decisions, and counsel patients and for researchers to design future studies.

Animal Models of Retinal Vein Occlusion.

Purpose: To provide a comprehensive and current review on the available experimental animal models of retinal vein occlusion (RVO) and to identify their strengths and limitations with the purpose of helping researchers to plan preclinical studies on RVO. Methods: A systematic review of the literature on experimental animal models of RVO was undertaken. Medline, SCOPUS, and Web of Science databases were searched. Studies published between January 1, 1965, and March 31, 2017, and that met the inclusion criteria were reviewed. The data extracted included animal species used, methods of inducing RVO, and the clinical and histopathologic features of the models, especially in relation to strengths, limitations, and faithfulness to clinical sequelae. Results: A total of 128 articles fulfilling the inclusion criteria were included. Several species were used to model human branch and central RVO (BRVO; CRVO) with nonhuman primates being the most common, followed by rodents and pigs. BRVO and CRVO were most commonly induced by laser photocoagulation and all models showed early features of clinical disease, including retinal hemorrhages and retinal edema. These features made many of the models adequate for studying the acute phase of BRVO and CRVO, although macular edema, retinal ischemia, and neovascular complications were observed in only a few experimental animal models (laser-induced model in rodents, pigs, and nonhuman primates, diathermy-induced model in pigs, and following intravitreal injection of PD0325901 in rabbits for BRVO; and in the laser-induced model in rodents, rabbits, and nonhuman primates, diathermy-induced model in nonhuman primates, following permanent ligation of the central retinal vein in nonhuman primates, and with intravitreal injection of thrombin in rabbits for CRVO). Conclusions: Experimental animal models of RVO are available to study the pathogenesis of this disease and to evaluate diagnostic/prognostic biomarkers and to develop new therapeutics. Data available suggest laser-induced RVO in pigs and rodents to be overall the best models of BRVO and the laser-induced RVO rodents the best model for CRVO.

Management of postoperative gastrointestinal leakage with autologous stromal vascular fraction.

To assess the efficacy of using autologous stromal vascular fraction (SVF) to promote healing of controlled fistula tracts in the management of postoperative upper gastrointestinal leakage. This is an experimental study conducted on 10 experimental rabbits. Animal models were divided into the SVF group which received an autologous SVF and the control group which did not receive the implantation. Surgery was performed on both groups to induce a gastric leak and create a controlled fistula tract between the leakage site in the stomach and the skin. After 2 weeks, surgery was performed on the SVF group to harvest, process and then implant the autologous SVF in the fistula tract. Animal models were followed up and their fistula tracts were evaluated for healing by gross and microscopic examination of the fistula tracts before the SVF implantation and at 24 hours, 1 week, 2 weeks and 3 weeks after implantation. The control group revealed no closure of fistula tracts by the 3(rd) week after implantation and there were no signs of inflammation or drainage. On the other hand, the SVF group showed signs of healing process with progressive closure of the fistula tract to about 95% by the 3(rd) week after implantation. The use of autologous SVF implantation to promote the healing of controlled fistula tracts seems to be a novel, safe and effective method in the management of postoperative upper gastrointestinal leakage. It could prevent reoperation and reduce hospital stay, morbidity and mortality. These results are promising and provide support for further clinical studies.

Abnormal Anatomical Variations of Extra-Hepatic Biliary Tract, and Their Relation to Biliary Tract Injuries and Stones Formation.

BACKGROUND: To determine the most common abnormal anatomical variations of extra-hepatic biliary tract (EHBT), and their relation to biliary tract injuries and stones formation. METHODS: This is a retrospective review of 120 patients, who underwent endoscopic retrograde cholangiopancreaticography (ERCP) and/or magnetic resonance cholangiopancreaticography (MRCP), between July 2011 and June 2013. The patients' ERCP and MRCP images were reviewed and evaluated for the anatomy of EHBT; the medical records were reviewed for demographic data, biliary tracts injuries and stones formation. RESULTS: Out of 120 patients, 50 were males (41.7%) and 70 were females (58.3%). The mean age was 54 years old (range 20 - 88). Abnormal anatomy was reported in 30% (n = 36). Short cystic duct (CD) was found in 20% (n = 24), left CD insertion in 5% (n = 6), CD inserted into the right hepatic duct (RHD) in 1.7% (n = 2), duct of Luschka in 3.33% (n = 4) and accessory hepatic duct in also 3.33% (n = 4). Biliary tract injuries were reported in 15% (n = 18) and stones in 71.7% (n = 86). Biliary tract injuries were higher in abnormal anatomy (P = 0.04), but there was no relation between abnormal anatomy and stones formation. CONCLUSION: Abnormal anatomy of EHBT was found to be 30%. The most common abnormality is short CD followed by left CD insertion. Surgeons should be aware of these common abnormalities in our patients, hence avoiding injuries to the biliary tract during surgery. The abnormal anatomy was associated with high incidence of biliary tract injury but has no relation to biliary stone formation.