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Objective: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI., Methods: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically., Results: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL-S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = -0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death ( p < 0.001)., Conclusion: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To evaluate the frequency and type of perioperative hemorrhagic complications associated with vitreoretinal surgery in patients undergoing systemic treatment with the newer anticoagulant and antiplatelet agents including rivaroxaban, apixaban, dabigatran, and prasugrel., Methods: Retrospective review of a cohort of patients being treated with anticoagulant and antiplatelet drugs, who underwent any vitreoretinal surgical procedure over a 2-year period., Results: Thirty-six eyes of 33 patients were identified who underwent vitreoretinal surgical operations while being treated systemically with anticoagulant and antiplatelet therapy. No eyes suffered perioperative complications of retrobulbar hemorrhage, suprachoroidal hemorrhage, or subretinal hemorrhage. Four eyes (11.1%) experienced postoperative vitreous cavity hemorrhage after which two eyes (5.5%) required repeat surgical intervention and two eyes (5.5%) cleared spontaneously., Conclusion: Although there is a relative risk to such surgery in patients who are taking novel oral anticoagulants, these findings suggest that patients may safely undergo vitreoretinal surgery while maintaining therapy with rivaroxaban, apixaban, dabigatran, and prasugrel.

Objective: To compare pars plana vitrectomy (PPV) with PPV and scleral buckle (PPV/SB) for repair of rhegmatogenous retinal detachment (RRD)., Design: A retrospective chart review., Participants: Patients who underwent PPV or PPV/SB for RRD repair at a single institution., Methods: A retrospective chart review of patients in two different treatment groups and analysis of the anatomic and functional results., Results: Single-surgery anatomic success was achieved in 31 of 37 (83.8%) phakic eyes that underwent PPV and in 66 of 68 (97.1%) phakic eyes that underwent PPV/SB (p = 0.0216). Among pseudophakic eyes, 42 of 48 (87.5%) in the PPV group and 62 of 66 (93.9%) in the PPV/SB group achieved single-surgery reattachment (p = 0.3175). Visual acuity improvement was marginally greater in the PPV group among phakic (p = 0.4898) and pseudophakic (p = 0.2465) eyes., Conclusions: PPV/SB may be associated with a decreased risk for retinal redetachment when compared to PPV for repair of phakic RRD. In pseudophakic eyes, the anatomic success rate between the two techniques appears to be similar., (Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To report the effect of intravitreal bevacizumab on visual acuity and central retinal thickness (CRT) in refractory diabetic macular edema., Patients and Methods: Records of 60 eyes of 54 consecutive patients who underwent intravitreal bevacizumab therapy for refractory diabetic macular edema were reviewed. All eyes received intravitreal bevacizumab 1.25 mg/0.05 mL, and 36 eyes underwent pretreatment and post-treatment optical coherence tomography. Mean follow-up was 7.4 months., Results: Pretreatment mean visual acuity plus or minus standard deviation was 0.71 +/- 0.28 logarithm of the minimum angle of resolution (LogMAR) Snellen letters. At final follow-up, mean visual acuity had improved to 0.66 +/- 0.30 LogMAR (P = .0543). Mean baseline CRT was 440 +/- 106 microm, and follow-up mean CRT was 386 +/- 129 microm (P = .008). Vitrectomized eyes had worse visual acuity and CRT outcomes (P = .002 and P = .028, respectively) compared with nonvitrectomized eyes., Conclusion: Intravitreal bevacizumab may provide a functional and anatomic benefit in eyes with persistent diabetic macular edema despite previous treatments., (Copyright 2010, SLACK Incorporated.)

Background and Objective: To compare the surgical outcome of scleral buckling (group 1) versus scleral buckling with pars plana vitrectomy (group 2) for the repair of macula-off rhegmatogenous retinal detachment without proliferative vitreoretinopathy., Patients and Methods: A retrospective chart review was performed., Results: Eighty-three patients were identified in group 1 and 63 patients in group 2. Presenting visual acuity was 4/200 in group 1 and 3/200 in group 2. Median duration of detachment prior to surgery was 5 days in group 1 and 6 days in group 2. There was no statistical difference in best-corrected (P = .59) or most recent (P = .75) visual acuity between groups. Median best-corrected visual acuity was 20/30 and median most recent visual acuity was 20/40 in both groups. Significantly more additional procedures were performed in group 1 than in group 2 (21.7% vs 7.9%, respectively; P = .024). The final reattachment rate was 96.4% in group 1 and 98.4% in group 2. Proliferative vitreoretinopathy developed in 15.7% of patients in group 1 and 4.8% in group 2 (P= .037)., Conclusion: Visual outcome of scleral buckling is similar to scleral buckling with pars plana vitrectomy for the treatment of macula-off rhegmatogenous retinal detachment in patients without proliferative vitreoretinopathy. Patients undergoing scleral buckling only are at an increased risk of developing proliferative vitreoretinopathy and requiring additional procedures., (Copyright 2009, SLACK Incorporated.)

Purpose: To define the role of intravitreal bevacizumab in individuals with choroidal neovascularization (CNV) resulting from Ocular Histoplasmosis syndrome (OHS)., Design: Retrospective chart review of a surgical therapy., Methods: We reviewed the course of 28 eyes of 28 patients who underwent intravitreal injection of bevacizumab for treatment of CNV secondary to OHS. Outcome was measured by pretreatment and posttreatment visual acuity (VA)., Results: The average pretreatment logarithm of the minimum angle of resolution (logMAR) VA was 0.65 (Snellen equivalent of 20/88). Mean follow-up was 22.43 weeks with an average of 1.8 intravitreal injections. Average final logMAR VA was 0.43 (Snellen equivalent of 20/54). Twenty eyes (71%) experienced an increase in central VA, whereas four eyes (14%) were unchanged and four eyes (14%) experienced a decrease in vision., Conclusions: Intravitreal bevacizumab may improve or stabilize VA in a significant majority of patients with neovascular complications of OHS (24 eyes [85.7%] in our study population).

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias.

Objective: To evaluate the risk of hemorrhagic complications associated with vitreoretinal surgery in patients whose warfarin sodium therapy was continued throughout the surgical period., Methods: A review of 1737 records of patients undergoing pars plana vitrectomy was conducted. Inclusion criteria included patients receiving warfarin therapy whose international normalized ratios (INRs) were elevated above normal values on the day of surgery. Intraoperative and postoperative hemorrhagic complications were documented., Results: Fifty-four patients underwent 57 vitreoretinal surgical procedures with warfarin therapy and were divided into groups as follows: group S with INRs of 1.20 to 1.49, values considered subtherapeutic; group B with INRs of 1.50 to 1.99, values considered borderline therapeutic; group T with INRs of 2.00 to 2.49, values considered therapeutic; and group HT with INRs of 2.50 or greater, values considered highly therapeutic. No patients experienced anesthesia-related or intraoperative hemorrhagic complications. Two (7.7%) of 26 eyes in group S and 2 (16.7%) of 12 eyes in group HT experienced postoperative hemorrhages. All of the patients with vitreous hemorrhages had spontaneous clearing without additional treatment., Conclusions: Many patients may safely undergo vitreoretinal surgery while maintaining therapeutic levels of warfarin anticoagulation. We experienced no intraoperative hemorrhagic complications; the 4 postoperative complications resolved spontaneously without persistent visual sequelae or the need for supplemental surgery.

Purpose: To review our experience with triamcinolone-assisted pars plana vitrectomy for internal limiting membrane (ILM) peeling for various retinal diseases., Methods: Twenty-one patients underwent surgery in which intraoperative triamcinolone acetonide (TA) was used. Indications for surgery included epiretinal membrane (3 patients), branch retinal vein occlusion associated with macular edema (2), traction retinal detachment (3), diabetic macular edema (4), vitreous hemorrhage with diabetic macular edema (4), macular hole (4), and cystoid macular edema (1)., Results: TA was useful in the removal of the ILM in all cases. There were no intraoperative complications or toxicity. The mean follow-up was 22 weeks (range, 9-30 weeks). Eleven patients improved by >or=2 Snellen lines, 1 lost >or=2 Snellen lines, and 9 were within 2 Snellen lines of preoperative vision at the last follow-up., Conclusions: The intraoperative use of TA improves visualization of ILMs associated with a variety of conditions. No intraoperative or postoperative complications were observed. TA-assisted removal of the ILM appears to be safe and cost effective. TA-assisted ILM peeling should be considered as an alternative to the use of intraoperative dyes.

Background and Objective: To describe the results of surgical treatment of peripapillary choroidal neovascularization in age-related macular degeneration as an option to both laser photocoagulation and photodynamic therapy., Patients and Methods: Retrospective review of patients with peripapillary choroidal neovascularization secondary to age-related macular degeneration who were not eligible for or refused laser photocoagulation. Patients without the diagnosis of age-related macular degeneration and those who had extension of their neovascularization subfoveally were excluded from the review., Results: Eleven patients total were identified who met the specified inclusion criteria. The male to female ratio was 4:7, with an age range of 63 to 94 years (mean = 78 years). The mean area of involved retina temporal to the optic disc was 5 clock hours, with the distance of the temporal edge of the lesion from the fovea ranging from 100 to 2,000 microm. The mean duration of follow-up was 23 months, with 27% (3 of 11) experiencing recurrent choroidal neovascularization. The preoperative and postoperative visual acuity ranges were both 20/25 to counting fingers. Sixty-four percent (7 of 11) of patients had stable or improved visual acuity postoperatively, with a mean visual acuity change of 1 line visual improvement., Conclusion: In cases where photodynamic therapy and laser photocoagulation are not indicated, the surgical treatment of peripapillary choroidal neovascularization secondary to age-related macular degeneration may prove beneficial.

Purpose: Voriconazole, a new generation triazole, has been shown to achieve therapeutic intraocular levels after oral administration. Caspofungin is the first approved agent from a new class of antifungals, the echinocandins. This series describes experience at two centers using these novel antifungals to treat endogenous fungal endophthalmitis., Design: Retrospective review., Methods: Treatment of five patients with Candida endophthalmitis are reviewed. Postmortem intraocular voriconazole concentrations on a sixth patient are presented as well., Results: All patients had systemic cultures positive for Candida species. Three patients had prompt resolution of intraocular mycosis with intravenous and oral voriconazole, caspofungin, or both. The fourth patient with bilateral disease responded well to i.v. voriconazole and caspofungin but had a recurrence when discharged on oral voriconazole and i.v. caspofungin. This patient had a bowel resection with an ileostomy; therefore, absorption of oral voriconazole may have been inadequate. Bilateral amphotericin B intravitreal injection ultimately treated this patient. The fifth patient received 100 microg/0.1 ml of intravitreal voriconazole (final vitreous concentration approximately 25 microg/ml) followed by oral voriconazole and responded favorably. Our sixth patient had multisystem failure and passed away 1 week after initiating intravenous voriconazole for non-ocular candidemia. Postmortem HPLC analysis of the aqueous and vitreous revealed voriconazole concentrations of 1.52 microg/ml and 1.12 microg/ml, respectively (MIC90 of Candida albicans is 0.06 microg/ml)., Conclusions: Voriconazole and caspofungin appear to be powerful weapons to add to the existing armamentarium against fungal endophthalmitis. Further studies are warranted to define precisely the role of these new agents alone or in combination with other antifungals.

Purpose: To determine the outcome of macular hole surgery in a diabetic population with no evidence of proliferative retinopathy., Methods: This is a retrospective chart review of 183 patients (194 eyes) undergoing pars plana vitrectomy for an idiopathic macular hole., Results: The anatomic closure rate for the diabetic patients without proliferative retinopathy was 93.8% (15/16), compared with 94.9% (169/178) for nondiabetic patients. A best corrected visual acuity of 20/50 or greater was obtained in 50% of diabetic patients (8/16), compared to 58.4% of nondiabetic patients (104/178). There was no difference in postoperative complications between the two groups., Conclusion: The anatomic closure rate and visual outcome after macular hole surgery in diabetic patients without proliferative retinopathy is comparable to that of nondiabetic patients.

Purpose: To determine the visual outcomes and complications after multiple vitrectomies for repeat diabetic vitreous hemorrhage., Methods: A retrospective review during a 4-year period of patients requiring multiple vitrectomies for nonclearing vitreous hemorrhages with at least a 6-month follow-up., Results: Of the 38 cases of multiple vitrectomies for diabetic vitreous hemorrhage, the initial visual acuity was 20/50 or better in 5%, between 20/60 and 20/400 in 37%, and worse than 20/400 in 58%. The final visual acuity after the last vitrectomy was 20/50 or better in 25%, between 20/60 and 20/400 in 47%, and worse than 20/400 in 28%. Patients had a mean improvement of 1.08 lines of visual acuity, and a statistically significant difference in logMAR visual acuity was noted when the last corrected visual acuity was compared with baseline acuity by way of paired t-testing. Although a trend toward visual improvement was noted in patients who underwent multiple vitrectomies, multivariate models failed to detect any association between number of surgeries or demographic variables and change in visual acuity., Conclusion: Multiple vitrectomies for recurrent diabetic vitreous hemorrhage can have a favorable anatomic outcome while maintaining ambulatory vision.

Purpose: To evaluate the anatomic closure rate and visual outcome in patients undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) enhancement., Design: Retrospective, noncomparative interventional case series., Participants: One hundred ninety-three consecutive patients (204 eyes) seen at the Barnes Retina Institute with the clinical diagnosis of macular hole who underwent PPV between January 1998 and December 2000., Intervention: A consecutive series of 97 patients undergoing PPV with or without unilateral epiretinal membrane removal without ILM peeling (group 1), 44 patients with PPV and ILM peeling without ICG (group 2), and 35 patients with ICG-assisted ILM peeling (group 3)., Results: Overall, 86.4% of the holes closed with one operation, with 75 of 97 (77.3%) eyes in group 1, 43 of 44 (97.7%) eyes in group 2, and 34 of 35 (97.1%) eyes in group 3 (chi(2)= 10.51, P = 0.007). Of the eyes that did not close, 18 patients in group 1 underwent repeat surgery, with 90 of 97 (92.8%) eyes ultimately achieving closure. Visual acuity after surgery was 20/50 or better in 55 of 97 (56.7%) patients, 31 of 44 (70.4%) patients, and 18 of 35 (51.4%) patients in groups 1, 2, and 3, respectively (chi(2) = 3.43, P = 0.18) and increased by 2 or more lines from their preoperative status in 63 of 97 (64.9%) patients, 34 of 44 (77.3%) patients, and 25 of 35 (71.4%) patients, respectively (chi(2)= 2.25, P = 0.32). Multivariate logistic regression demonstrated that use of ILM peeling during vitrectomy increases the chances of developing 20/50 vision or better (odds ratio [OR], 2.4; 95% confidence interval, 1.06-5.45; P = 0.04). No eyes received concurrent cataract extraction with macular hole surgery, but 75 of 166 (45.2%) required cataract extraction postoperatively. Complications included 20 retinal tears, 4 retinal detachments, and 34 patients with postoperative elevations in intraocular pressure (IOP; defined as IOP greater than 30 mmHg)., Conclusions: Although this study is limited by the shorter follow-up in patients undergoing ILM peeling with or without ICG relative to the control group, our experience indicates that the use of ILM peeling is associated with a statistically significant improvement in the rate of primary macular hole closure with a single operation.

Purpose: To evaluate the use of ocular photodynamic therapy (OPT) with verteporfin in patients with choroidal neovascularization (CNV) from ocular histoplasmosis syndrome (OHS) and to compare these results with those for a natural history group., Methods: A retrospective chart review was performed to identify cases of CNV secondary to OHS treated with OPT. Complete data were available for 38 of 41 eligible eyes. Data regarding the following variables were abstracted from the patient charts: demographic characteristics, previous surgery, angiographic features, number and timing of treatments with OPT, follow-up time, and visual acuity. The visual acuity results of eyes receiving photodynamic therapy were compared with those for a natural history cohort., Results: On average, OHS patients who received treatment developed 0.88 line of visual improvement. Visual acuity improved or stayed the same in 69% (22 of 32) of eyes, improved by > or = 2 lines in 44% (14 of 32), and improved by > or = 4 lines in 22% (7 of 32). Patients who received OPT were 2.07 times more likely to have improved or constant vision than were those in the natural history group as described in one retrospective series (odds ratio = 2.07; 95% confidence interval, 0.78-5.56; P = 0.162). Thirty-eight percent (12 of 32) of eyes had undergone submacular surgery for CNV before any OPT., Conclusions: Ocular photodynamic therapy with verteporfin may be beneficial in patients with CNV secondary to OHS, even in the setting of previous submacular surgery.

Purpose: To determine the risk of new retinal tear or detachment following cataract surgery in eyes that had undergone successful repair of phakic retinal tear or detachment., Methods: A computerized search of records of patients evaluated at the Barnes Retina Institute from 1990 to 2000 for a diagnosis of phakic retinal tear or detachment was accomplished. The records of successfully treated patients were analyzed by type of tear or detachment, method of treatment, and development of sequential new tears or detachment. Eyes that subsequently underwent cataract surgery were classified by presence and location of intraocular lens as well as operative complications, including capsular rupture, vitreous loss, or retained lens fragments. The frequency of developing new tears or detachment was calculated., Results: The 2,175 eyes identified were subdivided according to those that had undergone repair of retinal break (n = 1,415), subclinical retinal detachment (n = 396), or retinal detachment (n = 364). Of 371 eyes that underwent subsequent cataract surgery, 17 (4.6%) developed a new tear or detachment postoperatively. Factors indicative of higher postoperative risks included myopia, tear or detachment in the fellow eye, sequential onset of new breaks prior to cataract surgery, and complications of cataract surgery., Conclusion: In patients who had undergone prior repair of retinal breaks or detachment, cataract surgery was associated with a 4.6% incidence of new breaks or detachment. Cataract surgery appears to be an independent risk factor for retinal tears or detachments. Dilated retinal examination following cataract surgery is advisable in patients who have previously undergone repair of a phakic retinal tear or detachment.

Purpose: To report the intraoperative occurrence of massive intraocular suprachoroidal hemorrhage associated with Valsalva maneuver., Methods: Retrospective, multicenter study of patients who developed massive choroidal hemorrhage associated with Valsalva maneuver during vitrectomy., Results: Massive intraoperative suprachoroidal hemorrhage in seven patients (seven eyes) involved three men and four women with a median age of 52 years (range, 26 to 82 years). General anesthesia was used in six of seven cases. Coughing or "bucking" on the endotracheal tube during general anesthesia or severe coughing during the one vitrectomy performed under local anesthesia was associated with massive suprachoroidal hemorrhage. In five of seven eyes, this occurred near the end of surgery, after air-fluid exchange but before sclerotomy closure. Scleral plugs were immediately placed, and sclerotomy closure was performed exigently. Immediate posterior sclerotomy was performed on five of seven eyes; an additional patient underwent posterior sclerotomy postoperatively. After median follow-up of 18 months (range, 3 to 36 months), final visual acuity was no light perception in four eyes, light perception in one eye, 20/250 in one eye, and 20/20 in one eye. Four eyes became phthisical., Conclusions: Valsalva maneuver during pars plana vitrectomy may result in massive suprachoroidal hemorrhage with disastrous visual consequences. Precautionary measures to prevent coughing or "bucking" on the endotracheal tube during general anesthesia, or a prolonged episode of coughing during local anesthesia, may prevent this potentially devastating complication.

Purpose: To review our experience with vitrectomy surgery techniques for the treatment of traumatic macular holes and the biomicroscopic and surgical findings., Design: Retrospective noncomparative, multicenter, case series., Participants and Intervention: Twenty-five patients with traumatic macular hole underwent surgical repair., Intervention: Vitrectomy with membrane peeling and gas injection followed by prone positioning for 7 to 14 days., Main Outcome Measures: Postoperative evaluation included visual acuity testing, closure of the macular hole, and ocular complications., Results: The macular hole was successfully closed in 24 of 25 cases (96%). The visual acuity improved two or more lines in 21 (84%) cases, and 16 (64%) achieved 20/50 or better vision., Conclusions: Vitrectomy surgery can successfully close macular holes associated with trauma and improve vision.