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To review the autologous retinal transplantation surgical technique, indications, rationale, and current outcomes of data published to date.Review of surgical technique, preoperative and postoperative best-corrected visual acuity, and macular hole (MH) closure rate in studies with at least five eyes.The weighted average macular hole closure rate is 88%, with a MH closure rate ranging from 66.7% to 100%. The weighted average best-corrected visual acuity improved from mean logarithm of the minimum angle of resolution 1.35 (Snellen equivalent of 20/450) preoperatively to mean logarithm of the minimum angle of resolution 1.02 (Snellen equivalent of 20/210) postoperatively. From the largest autologous retinal transplantation case series, 37% of patients gained 3 or more lines of visual acuity after autologous retinal transplantation for primary or refractory MHs and 74% gained 3 or more lines of visual acuity after autologous retinal transplantation for MH-retinal detachments. Functional improvement including negative Watzke-Allen sign and conversion from positive to negative scotoma was reported in large case series.Autologous retinal transplantation is a promising technique for closure of large and refractory MHs otherwise difficult to repair with conventional techniques. This technique may allow for replacement of neural tissue in the macula through cell rehabilitation and regeneration through presumed ectopic synaptogenesis, retinal progenitor cell differentiation and integration, and/or retinal progenitor cell material transfer to host neurons.

Introduction: Despite consistent use of anti-vascular endothelial growth factor (anti-VEGF), prognosis of large, fovea-involving submacular hemorrhage (SMH) has remained guarded, particularly in pa...

BACKGROUND AND OBJECTIVE: To describe the ultra-widefield (UWF) imaging characteristics of patients with degenerative peripheral retinoschisis (DPR) using Optomap technology. PATIENTS AND METHODS: In this multicenter, retrospective, noncomparative, consecutive case series, eligible patients underwent detailed retinal examination including indirect ophthalmoscopy. UWF fundus imaging, including color fundus photography, autofluorescence, and angiography, was performed using standardized protocols and findings were recorded and reviewed and analyzed. RESULTS: A total of 35 patients (58 eyes) with DPR were identified who underwent 55 sessions of UWF imaging. Mean age was 65 years, and the inferotemporal quadrant was most commonly affected (74% of eyes). Of these patients, 31 underwent fluorescein angiography and 90% of these studies illustrated abnormalities in the area affected by the schisis. The most common finding was retinal vascular leakage originating from the deep capillary plexus observed in 29 eyes (93.5%). CONCLUSIONS: UWF imaging enables a more detailed identification of the clinical features associated with DPR and provides simple, practical, and noninvasive tools to monitor progression of disease. The breadth of retinal vascular complications identified with fluorescein angiography may suggest an important vascular component associated with the pathogenesis of this entity. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:557–564.]

Purpose To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. Design Multicenter retrospective cohort study. Methods All eyes receiving intravitreal injection of 0.5 mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. Results A total of 243 754 intravitreal 0.5 mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015%; 1 in 6534 injections) and 2 cases of culture-positive endophthalmitis occurred (0.0026%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95% confidence interval 0.31-1.12; P = .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95% confidence interval 0.045-0.82; P = .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P = .0062). Oral-associated flora was found in 27.3% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. Conclusion In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes.

BACKGROUND: Closure of traumatic macular hole (TMH) can be achieved spontaneously or by surgical intervention. Thus far, there exist no prospective comparative studies that have analyzed the difference between the two modalities. This study aimed to compare the anatomical and visual recovery of eyes with TMH following either an immediate vitrectomy or six-month observation. METHODS: This was a multicenter prospective comparative study. Eight centers participated in the study. Patient data from 40 eyes with a recent history of blunt ocular trauma and newly formed full-thickness TMH were recruited in this study. The participating patients selected between an early vitrectomy or a six-month observation after a doctor explained the potential benefits and risks of both strategies in an unbiased manner. Twenty-five patients underwent an immediate vitrectomy, and 15 patients received six-month observation. Patients were assessed by spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA). RESULTS: Closure rates were 66.7% for the observational group, and 100% for the surgical group (P=0.002). There were no vision-threatening ocular complications in both groups. For the observational group, the mean closure time was 2.5±1.6 months, and 80% of the hole closure occurred within 3 months; cystic edema on the edge of the hole at baseline was significantly more frequent in the non-closed subgroup than in the closed subgroup (P=0.03). There were no significant differences in the foveal microstructure and in the final visual outcome between the spontaneously closed cases and the surgically closed cases. CONCLUSIONS: TMH had a moderately high incidence of spontaneous closure, but an immediate vitrectomy achieved an even higher closure rate. Vitrectomy was effective and safe to treat TMH, while a 3-month observation for spontaneous closure may be an alternative modality for TMH management. Cystic edema on the edge of the hole may be an unfavorable factor for the spontaneous closure of TMH.

Purpose:This work evaluates the effects of combined intravitreal antivascular endothelial growth factor (anti-VEGF) and modified panretinal photocoagulation (PRP) for management of proliferative diabetic retinopathy (PDR).Methods:This retrospective case series included 37 eyes of 33 patients with high-risk PDR. Anti-VEGF injections (≥ 2) were followed by modified, midperipheral PRP performed in 2 or more sessions. Visual and anatomic outcomes were tracked for 1 year after treatment. Regression analysis was performed for factors predictive of final outcomes.Results:Mean visual acuity (VA) at initial and final visit were 20/50 and 20/40 ( P = .22), respectively, over a mean follow-up duration of 341.4 days. Central foveal thickness decreased from 321.8 µm to 258.6 µm ( P = .01). Resolution of PDR was achieved in 94.6% of eyes, with 5.4% of eyes requiring additional anti-VEGF for persistent neovascularization. Final VA was significantly associated with baseline VA, VA at 1 month, and any adverse anatomical events. Treatment noncompliance was present in 24.3%; compliance decreased with increasing medical comorbidities, but was not significantly associated with final VA.Conclusions:Combination of anti-VEGF and modified PRP preserved VA and yielded PDR regression in the majority of eyes. This combination provides rapid PDR regression with anti-VEGF while achieving durable disease suppression in this real-world cohort without traditional PRP.

Purpose: The purpose of this article is to report the characteristics of patients with retinoschisis-related retinal detachments and to summarize their clinical outcomes after surgical repair. Methods: A single-center interventional case series of 37 eyes from 35 patients who underwent surgery to repair a retinoschisis-related retinal detachment between January 1, 2009 and January 1, 2017 was conducted. Results: The mean ± SD age at the time of the first retinal detachment repair was 63 ± 13 years. As the initial surgery, scleral buckle was performed in 14 eyes, scleral buckle + vitrectomy in 14 eyes, and vitrectomy in 9 eyes. The single-operation success rate for the entire cohort was 65% (24/37), and the final anatomic success rate was 97% (36/37). Among eyes requiring more than 1 surgery, 46% (6/13) developed proliferative vitreoretinopathy. Best-corrected visual acuity improved or remained stable after 1 year of follow-up in the majority (n = 27, 73%) of eyes. The mean (SD) number of surgeries required to achieve the final anatomic and visual result was 1.8 (1.2) for all eyes (range, 1-5 surgeries). Conclusion: The single-surgery success rate for retinoschisis-related retinal detachments was lower than that reported for typical rhegmatogenous retinal detachments, and the incidence of proliferative vitreoretinopathy was higher. When counseling patients with retinoschisis-related retinal detachments, it is important to caution them that they may require more than 1 surgery to achieve anatomic success.

Purpose To describe surgical outcomes and structural characteristics of intraocular lenses (IOLs) implanted with transconjunctival sutureless intrascleral (SIS) fixation in human eyes. Design Retrospective interventional surgical case series involving live and cadaveric human eyes. Methods In this study, we investigated the surgical outcomes and structural anatomy of secondary IOLs implanted with the SIS technique in human eyes. All cases involving SIS IOL fixation performed at a single academic center from January 1, 2012, through July 30, 2016, were reviewed to describe the surgical technique, common indications, clinical outcomes, and the rate of common operative complications. To investigate the structure of SIS-fixated IOLs in vivo, slit-lamp biomicroscopy, ultrasound biomicroscopy, and intraoperative endoscopy were analyzed to describe anatomical outcomes. The primary anatomical outcomes were the optic pupillary centration and location of haptic externalization. Results were correlated with cadaveric human eyes that underwent the SIS-IOL technique. Cadaveric eyes were imaged and analyzed using high-resolution photography for centration, stress measurements at the haptic-optic junction, and qualitative descriptors of IOL optic and haptic position. Results A total of 122 consecutive patients who underwent IOL placement using SIS technique were included in the study with mean follow-up of 1.52 years (range, 0.4-4.5 years). The majority (75%) of patients received a new 3-piece IOL for primary aphakia or after IOL exchange. The other patients (25%) had a dislocated 3-piece IOL that was rescued using the SIS technique. Preoperative mean Snellen visual acuity was 20/633 (logarithm of the minimum angle of resolution = 1.501). At the final visit, the mean best-corrected visual acuity was 20/83 (logarithm of the minimum angle of resolution = 0.6243) and final mean spherical equivalent was -0.57 diopters. The most common complications were vitreous hemorrhage (22% of eyes), which resolved spontaneously in most cases, and cystoid macular edema. The rates of IOL dislocation, IOL decentration, haptic erosion, IOL tilting, iris capture, and endophthalmitis were low. Intraoperative endoscopy and ultrasound biomicroscopy demonstrated a securely fixated IOL and well-centered optic without iris or ciliary body touch. Structural study of cadaveric eyes confirmed IOL optic and haptic anatomy observed during live human surgery. The ab interno haptic insertion was the anterior pars plana, away from the iris, ciliary processes and ora serrata. The degree of haptic externalization was correlated with the degree of strain on the haptic-optic junction. The angle of the haptic-optic junction in SIS-fixated IOLs (33.97°) was not significantly different compared with overlaid native nonfixated IOL (32.93°) but increased slightly with degree of haptic tip externalization (36.26 and 39.16 for 2 and 3 mm haptic externalizations, respectively). Conclusion In this comprehensive study, we demonstrate the surgical outcomes achieved with SIS fixation of IOLs. Surgical and postoperative complications do occur, albeit at a low rate, and can effectively be managed with excellent anatomical and visual outcomes. The structural and anatomical data in this study may help guide SIS placement and optimize long-term surgical results.

To investigate the efficacy of the intravitreal dexamethasone implant as the treatment for recalcitrant macular edema after successful rhegmatogenous retinal detachment repair.A retrospective review of the medical records was performed on 17 consecutive patients (17 eyes) with recalcitrant macular edema associated with rhegmatogenous retinal detachment repair who were treated with a single or multiple injections of an intravitreal dexamethasone 0.7-mg implant (Ozurdex; Allergan Inc) at two centers. Main outcomes of the study were change in logarithm of the minimum angle of resolution visual acuity, measurement of central foveal thickness, and macular cube volume as measured by spectral domain optical coherence tomography and frequency of complications.The mean age was 67 years (range, 51-78 years). All 17 patients received previous topical therapy and 12 of them had previous administration of intravitreal triamcinolone with persistence of macular edema. Baseline mean best-corrected visual acuity was 20/100 (logarithm of the minimum angle of resolution 0.75; range, 0.18-1.3 ±0.37) in the affected eyes. There was a statistically significant improvement in best-corrected visual acuity at 1 month (P0.001) and 3 months (P = 0.01). Mean baseline central foveal thickness was 505 μm, and mean macular cube volume was 10.62 mm. There was a statistically significant decrease in central foveal thickness and macular cube volume at 1 month (505-290 μm, P = 0.013 and 10.62-9.13 mm, P0.0001) and 3 months (P = 0.01). All patients developed recurrence of macular edema at 3 months, which required retreatment. The average number of implants was 4 (range, 1-14). No adverse effects such as retinal detachment or endophthalmitis occurred. Two patients experienced an increase in intraocular pressure that was controlled with topical therapy.Macular edema that occurs in eyes after successful repair of rhegmatogenous retinal detachment can be chronic and recalcitrant, and may be successfully and safely treated with the dexamethasone intravitreal implant.

PURPOSE Fibrovascular contraction and tractional retinal detachment (TRD) are recognized complications associated with the use of anti-vascular endothelial growth factor agents in vasoproliferative vitreoretinopathies. The authors characterize TRDs that developed after intravitreal bevacizumab or ranibizumab therapy for vascularly active retinopathy of prematurity. METHODS This is an international, multicenter, interventional, retrospective, case series. Thirty-five eyes from 23 infants were included. Inclusion required anti-vascular endothelial growth factor treatment of Type 1 retinopathy of prematurity with progression to TRD. RESULTS Mean gestational age was 26 ± 2 weeks, and mean birth weight was 873 ± 341 g. Mean postmenstrual age on the day of injection was 35 ± 2 weeks. Retinal detachment was noted a mean of 70 days (median, 34; range, 4-335) after injection. Eleven percent detached within 1 week, 23% within 2 weeks, and 49% within 4 weeks. The highest stage of retinopathy of prematurity noted was 4A in 29%, 4B in 37%, and 5 in 34% of eyes. Time to RD negatively correlated with postmenstrual age at the time of injection (Rho = -0.54; P < 0.01). Three TRD configurations were observed: 1) conventional peripheral elevated ridge or volcano-shaped Stage 5 detachment, 2) midperipheral detachment with tight circumferential vectors, and 3) very posterior detachment with prepapillary contraction. Full or partial reattachment was achieved with surgical intervention in 86% of eyes. CONCLUSION Progressive atypical TRD may occur after anti-vascular endothelial growth factor injections for retinopathy of prematurity. The configuration of the detachment varies with the extent of primary retinal vascularization present at the time of treatment.

Purpose: To report the clinical findings in patients ≥100 years old who have age-related macular degeneration (AMD). Methods: We identified patients ≥100 years old who had non-neovascular AMD, neovascular AMD or both. Results: Sixty-two patients were included. The mean (SD) age was 102 (1.4) years (range, 100-106 years). Most patients were white (n = 51, 82%), women (n = 51, 82%), and had at least 1 eye affected by neovascular AMD (n = 55, 89%). The mean Snellen visual acuity (VA) among eyes with neovascular AMD was worse than that for eyes with non-neovascular AMD (20/600 [range, 20/40-hand motions] vs 20/250 [range, 20/20-hand motions], respectively, P = .03). Eyes with an intact subfoveal ellipsoid zone (EZ) had much better mean VA than eyes with an absent or disrupted EZ (20/50 vs 20/500, P = .002). Conclusion: Most centenarians with AMD in our cohort had the neovascular form, and these individuals tended to have poorer vision than those with non-neovascular AMD. The presence of an intact subfoveal EZ is associated with better VA in eyes with neovascular or non-neovascular AMD compared to eyes with an absent or disrupted EZ.

Scleritis is defined as an infectious or noninfectious inflammation of the sclera that can be broadly categorized according to anatomic location (ie, anterior or posterior) and whether the process is necrotizing or non-necrotizing. Treatment for scleritis is dictated by the etiology of the inflammation, with infectious forms requiring treatment of the inciting agent and noninfectious forms requiring treatment of the underlying inflammation with immunosuppression. Pharmacotherapy for noninfectious scleritis can be classified according to delivery route (eg, local or systemic) and mechanism of action (eg, biologic or nonbiologic). This review will briefly summarize the classification scheme for scleritis before reviewing in depth both systemic and local pharmacotherapies that can be used to effectively treat an eye afflicted by either infectious or noninfectious scleritis. Traditional anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs, steroids, and immunomodulatory therapy will be discussed, as well as newer biologic therapies such as antitumor necrosis factor alpha and anti-CD20 agents.

Intraocular lenses (IOLs) can have inadequate support for placement in the capsular bag as a result of ocular trauma, metabolic or inherited conditions such as Marfan syndrome or pseudoexfoliation, or complicated cataract surgery. Surgical options for patients with inadequate capsular support include alternative placement of the IOL in the anterior chamber, fixation to the iris, or fixation to the sclera. The surgical techniques for each of these approaches have improved considerably over the last several decades resulting in improved visual and ocular outcomes. If no capsular or iris support exists, the surgeon can fixate an IOL to the sclera or the patient can remain aphakic. IOLs can be fixated to the sclera using sutures or by tunneling the IOL haptics into the sclera without sutures. This review summarizes the preoperative considerations, surgical techniques, outcomes, and unique complications associated with implantation of scleral-fixated IOLs.

Purpose:With multiple anti–vascular endothelial growth factor (VEGF) and steroid therapies available for diabetic macular edema (DME), there is a need for early determination of the best treatment for a particular patient to prevent irreversible vision loss from chronic DME. In this study, we classify patients as responders or nonresponders to anti-VEGF monotherapy in the treatment of DME after a single anti-VEGF injection.Methods:The study was designed as a single-center, retrospective, interventional case series. We included patients who received 3 consecutive monthly injections with the same anti-VEGF agent. We excluded patients who were treated for DME in the preceding 3 months with any form of anti-VEGF therapy. Visual acuity and central retinal thickness (CRT) data were followed for 1 year. Receiver operating characteristic (ROC) curve analysis was performed in order to identify the cutoff values for identifying responders.Results:One hundred seven eyes were reviewed, with 40 eyes of 34 patients meeting all inclusion criteria. Based on ROC curve analysis, a reduction in CRT by >15% at 1 month identified eyes that responded to treatment and had a >25% reduction in CRT at 3 months (sensitivity, 0.75; specificity, 0.92).Conclusion:Diabetic macular edema eyes that have early response to anti-VEGF treatment by reduction in CRT will have significant response to treatment by 3 months.

Purpose To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy. Methods Observational case series involving single family and literature review. Results A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Both patients were managed with laser photocoagulation. Eight years after the initial presentation, both siblings developed pancytopenia secondary to bone marrow failure. Laboratory work-up revealed severely shortened telomere length in both patients, and genetic testing revealed a missense mutation in the gene that encodes the reverse transcriptase component of telomerase, confirming the diagnosis of dyskeratosis congenita. The father of both children was a carrier of the same mutation, who exhibited marked retinal vascular tortuosity of the second-order vessels. Conclusion Dyskeratosis congenita is a severe multisystem disorder, which should be considered in cases of pediatric exudative retinopathies with concurrent signs and/or symptoms of bone marrow failure.

Purpose: To evaluate the efficacy of a dexamethasone intravitreal implant in combination with intravitreal anti-vascular endothelial growth factor (VEGF) agents for treatment-resistant neovascular age-related macular degeneration (nvAMD). Methods: This study was designed as a single-center, retrospective interventional case series. Consecutive patients with treatment-resistant nvAMD underwent simultaneous combined injection of anti-VEGF agent and dexamethasone intravitreal implant. Eighteen patients with mean age of 81.5 years were included. Patients received an average of 26.3 anti-VEGF injections before dual therapy, with a mean follow-up of 8.2 months after dual therapy. Results: Dual therapy produced a significant mean decrease in central foveal thickness (126.3 μm), compared to a mean increase in 29.9 μm when treated with anti-VEGF monotherapy ( P = .0017). Patients also had a mean decrease in macular cube volume of −0.85 mm3 with dual therapy compared to anti-VEGF monotherapy ( P = .0014). There was a moderate correlation between the number of prior anti-VEGF injections and the magnitude of anatomic response, suggesting that shorter disease duration may positively influence response to combined treatment. Although there was a slight trend toward improved mean visual acuity after dual therapy, these differences did not reach statistical significance. Nevertheless, with combination treatment, 33% of patients gained 1 or more lines of vision. Dual therapy resulted in a significantly lower number of required anti-VEGF injections (4.25 vs 5.33) and an increase in the anti-VEGF injection-free interval to 1.41 months from 1.12 months during the 6 months following dual therapy compared to the same interval before dual therapy. Dual therapy was well tolerated; 2 eyes developed mild intraocular pressure elevation effectively managed with topical therapy and 1 patient developed worsening cataract. Conclusions: Combined treatment of anti-VEGF with dexamethasone intravitreal implant is a viable alternative for treatment-resistant nvAMD and may reduce treatment burden. Earlier treatment with dual therapy may be beneficial to maximize anatomic and visual outcomes in these patients.

Secondary intraocular lens (IOL) placement in uveitic eyes is challenging. We describe a series of sclerally fixated IOLs using a transconjunctival sutureless (SIS) technique in eyes with history of uveitis.This is an interventional, retrospective, consecutive case series.Five patients with a history of well-controlled uveitis were included. All underwent vitrectomy, with removal of residual lens fragments if necessary. All received pre-, intra- and perioperative steroids, which were slowly tapered over the weeks after the surgery. If possible the dislocated IOL was rescued; otherwise, insertion of a new three-piece IOL was made. Postoperatively, all IOLs remained centered and haptics covered by conjunctiva without dislocation, erosion, or scleral thinning. There were no significant complications related to the surgery. Overall, the mean preoperative visual acuity was improved from logMAR 2.09 preoperatively to 0.59 postoperatively, which was statistically significant (p = 0.015). All eyes were deemed quiet at follow-up and none required escalation of therapy for long-term uveitis control.SIS IOL fixation is a safe and effective option for well-controlled uveitic eyes.

BACKGROUND AND OBJECTIVE: The authors report the technique of using the 27-gauge (G) vitreous cutter through 25-G valved cannulas to allow hybrid instrumentation of both gauges. PATIENTS AND METHODS: Vitrectomy is initiated with standard placement of 25-G valved cannulas, followed by insertion of a 27-G vitreous cutter through the 25-G cannulas. RESULTS: The hybrid procedure emphasizes the advantages of both platforms: The 25-G cutter is more efficient for core vitrectomy and is more rigid to facilitate peripheral vitrectomy; the 25-G platform enjoys a wider armamentarium of instrumentation options; and the smaller profile of the 27-G cutter can be maneuvered more easily into tight surgical planes to act analogous to vertical scissors, with the added benefits of aspiration and spatula-like features. The authors illustrate this technique in three cases: diabetic tractional retinal detachment with dense plaques, posterior stage 4B retinopathy of prematurity, and sutureless scleral fixation of an intraocular lens. CONCLUSIONS: Hybrid use of the 25-G and 27-G platforms offers greater versatility for the management of complex vitreoretinal conditions. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:352–355.]

Transconjunctival sutureless intrascleral fixation is an important surgical option for secondary intraocular lens (IOL) implantation. In this report, the authors describe the technique of using a 27-gauge platform to perform pars plana vitrectomy, lensectomy, and sutureless scleral IOL fixation in a patient with crystalline lens dislocation secondary to Marfan's syndrome. Case report and detailed description of the surgical technique are discussed. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:376–379.]

Capillary dropout is a common sequela of endothelial cell dysfunction that underlies the pathology of multiple retinal vascular diseases, including familial exudative vitreoretinopathy (FEVR). Wide-field fluorescein angiography allowed for identification of areas of capillary inflammatory changes and late-phase angiographic posterior and peripheral vascular leakage (LAPPEL). We propose LAPPEL as a precursor in pathogenesis of capillary dropout and a marker of endothelial cell inflammation in the retina. The authors describe a case of FEVR with significant macular edema associated with LAPPEL, which was successfully treated with topical and intravitreal steroids. The implication for disease mechanism and potential future treatment applications are also discussed. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:288–292.]

Purpose: To describe a technique to reduce intraocular lens (IOL) tilt after sutureless intrascleral (SIS) fixation. Methods: Case report with review of surgical technique. Results: We report a technique that can be used to correct IOL tilt that may rarely accompany SIS IOL fixation. The procedure involves placing pupil-spanning polypropylene sutures on either side of the IOL optic to keep the optic parallel to the plane of the iris. Conclusion: Sutureless intrascleral IOL tilt correction can be achieved using polypropylene suture, thus obviating the need for more invasive surgical maneuvers, such as IOL exchange.

To describe vitreoretinal surgical technique of using autologous platelet-rich plasma to aid in surgical repair of optic pit maculopathy refractive to previous vitrectomy.A case of an 18-year-old woman presenting with serous macular detachment secondary to optic pit is reported. Patient had previously undergone vitrectomy and peripapillary laser, but had recurrence of subretinal fluid and worsening visual acuity. Autologous platelet-rich plasma was harvested from the patient's blood and purified using Arthrex ACP kit (Arthrex, Inc, Naples, FL). Repeat pars plana vitrectomy was performed with internal limiting membrane peeling extending to the optic nerve. Platelet-rich plasma was layered over the pit and long-acting gas tamponade performed with face-down positioning.At 8 months of follow-up, subretinal fluid was resolved, the connection between optic pit and subretinal space collapsed and the ellipsoid zone near completely reconstituted on optical coherence tomography. The patient's vision improved significantly from 20/100 to 20/50, which is largely limited by posterior subcapsular cataract.Platelet-rich plasma can augment anatomical and visual outcomes in surgical repair of optic pit maculopathy.

To determine whether haptic flanging during 27-gauge sutureless intrascleral fixation of intraocular lenses (IOLs) increases IOL stability and to report the short-term clinical outcomes of sutureless intrascleral surgery using 27-gauge trocar cannulas with haptic flanging.Retrospective surgical case series using live and cadaveric human eyes.In the cadaveric experiment using five eyes, flanged haptics required more force to dislocate the IOL compared with unflanged haptics (14 ± 4 vs. 3 ± 1 g, P = 0.03). The clinical series included 52 eyes from 52 patients. The average age at the time of surgery was 73 ± 14 years, with a mean follow-up of 27 ± 19 weeks. The most common indication for surgery was IOL dislocation/subluxation (n = 43, 83%). Mean visual acuity improved from 20/140 preoperatively to 20/50 at postoperative Month 1 (P0.001). The most common postoperative issue was intraocular pressure elevation (n = 12, 23%). Two patients (4%) needed a reoperation for IOL dislocation.Haptic flanging during 27-gauge sutureless intrascleral surgery creates a more stable scleral-fixated IOL compared with the traditional unflanged technique based on a cadaveric human eye study. In addition, this variation of sutureless intrascleral surgery seems safe and effective for patients who require secondary IOLs.

Purpose We report a case of congenital toxoplasmosis associated with retinal detachment. Methods A 9-month-old white boy presented a unilateral tractional retina detachment associated with congenital toxoplasmosis retinochoroiditis. Results The diagnosis is supported by positive IgG (>400) for toxoplasmosis and intracranial calcification on magnetic resonance imaging, along with positive family history of Toxoplasma infection in the mother. Conclusion Tractional retinal detachment is an infrequent and unconventional presentation of congenital Toxoplasma infection. Inflammatory interference with normal sequence of vitreous development may explain pathogenesis of tractional retinal detachments in the setting of congenital ocular toxoplasmosis.

Purpose To report the clinical and histopathological findings of a patient with bilateral keratomalacia arising from severe vitamin A deficiency from panic disorder-related malnutrition. Methods Case report. Results A 47-year-old male with panic disorder presented with 1 month of painful vision loss sequentially affecting the right and left eyes. He exhibited bilateral conjunctival xerosis with complete corneal melt in the right eye and a large corneal epithelial defect with underlying anterior chamber inflammation in the left eye. Laboratory investigation revealed undetectable serum vitamin A levels attributed to self-induced vomiting and starvation. He was treated with high-dose vitamin A, but the right eye required enucleation. The histological findings are reported. Conclusions Vitamin A deficiency in the absence of organic gastrointestinal abnormalities is exceedingly rare in the developed world. A strong index of suspicion and thorough review of systems are invaluable in evaluating patients with unexplained corneal melt.

Purpose To derive novel insights into the pathophysiology of vancomycin-related hemorrhagic occlusive retinal vasculopathy (HORV) through a careful clinicopathologic correlation. Methods We retrospectively reviewed the clinical and pathologic course of 2 consecutive patients who developed HORV. The clinical history, multimodal imaging, ultrasound biomicroscopy (UBM), and intraoperative and histologic findings are reported. Results Both patients presented with decreased vision and eye pain within 1 week following otherwise uncomplicated cataract extraction and were diagnosed with HORV after endophthalmitis was ruled out. Both patients presented with significant ocular discomfort that progressively worsened, and both experienced a dismal visual outcome despite early aggressive medical and surgical therapy. One patient requested enucleation for a blind and painful eye. Upon histologic examination of this eye, the iris and ciliary body appeared to be infarcted with separation of the iris and ciliary epithelia from their adjacent stromal components. These findings were corroborated by UBM of the second patient. Histologic examination of the posterior segment demonstrated severe hemorrhagic necrosis of the neurosensory retina and an occlusive nonarteritic vasculopathy of the retina and choroid. The choroid was thickened by prominent nongranulomatous chronic inflammation accompanied by a glomeruloid proliferation of small vessels. The inflammatory infiltrate was almost exclusively confined to the choroid and consisted of predominantly T cells. There was conspicuous absence of inflammatory cells in the retina and no histologic evidence of leukocytoclastic vasculitis. Conclusions HORV is a rare condition that can lead to profound vision loss. Significant ocular pain can be a presenting sign of HORV in cases with severe iris and ciliary body ischemia. Although it has been suggested that HORV is a form of leukocytoclastic retinal vasculitis, the histologic findings herein indicate that the pathophysiology is more complex. It is grounded in a necrotizing retinal vasculopathy in the absence of retinal vasculitis, chronic nongranulomatous choroiditis, and an unusual glomeruloid proliferation of endothelial cells in the choroid and elsewhere in the eye.

BACKGROUND AND OBJECTIVE: To describe a novel technique of scleral indentation and transillumination for single-surgeon, unassisted vitrectomy and vitreous base shaving enhanced with a digital heads-up display system (NGENUITY 3D Visualization System; Alcon, Fort Worth, TX). PATIENTS AND METHODS: This technique was utilized in six eyes of six patients during vitrectomy surgery for common vitreoretinal surgical diagnoses. In each case, the transillumination was performed with the traditional intraocular light pipe set at 100% power, placed obliquely just posterior to the vitreous base insertion, with or without a transillumination adapter. The visualization of the vitreous cavity was digitally enhanced using a heads-up display system (NGENUITY 3D) with light amplification settings increased to near-maximal gain. In each case, the adequacy of the surgical view was judged intraoperatively by two independent surgeons who shared the same surgical view as the primary surgeon. RESULTS: In this series, the surgical view provided by the scleral transillumination was deemed adequate to safely perform surgery in five of six cases. In the one patient in whom this was not the case, vitrectomy was completed using traditional endo-illumination and scleral depression performed by a skilled assistant. Lighter fundus pigmentation, myopia, thin sclera, and absence of dense peripheral media opacities were associated with improved view with scleral transillumination. There were no intraoperative complications. CONCLUSION: Digitally enhanced scleral transillumination affords surgeons another option for safe and effective simultaneous scleral depression and illumination for unassisted peripheral vitrectomy. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:436–439.]

To discuss the latest advances and controversies in the diagnosis and care of infants with retinopathy of prematurity (ROP).Literature review.Retinopathy of prematurity remains a major global issue. Industrialized nations now treat profoundly premature infants with posterior and aggressive disease, and middle-income nations are experiencing ROP epidemics. Remote digital imaging may address the decreasing ratio of ROP providers to premature infants, in addition to improving patient care. Widefield angiography, optical coherence tomography, and the Wnt signaling pathway have provided new insights into ROP pathogenesis. Anti-vascular endothelial growth factor treatment is increasing in popularity, but the dearth of information to guide dosing, unpredictable reactivation, persistent vascular abnormalities, the "crunch" phenomenon, and the presently unknown effects of systemic vascular endothelial growth factor suppression remain issues to continue investigating. Neurodevelopmental delay has been raised as a potential consequence, but the evidence currently is weak. Vitrectomy is the treatment of choice for Stages 4 and 5. Illumination techniques, ab interno incisions, plasmin-assisted vitrectomy, staged surgery in the interest of corneal clearing for advanced Stage 5, and immediate sequential bilateral vitreoretinal surgery, are useful techniques.We are making progress in ROP management. Our goal as clinicians is to continue expanding the boundaries of our abilities to keep this blinding disease in check globally.

Several studies have validated the role of telemedicine as a new powerful screening and diagnostic tool for retinal disorders, such as diabetic retinopathy and retinopathy of prematurity. With regard to retinopathy of prematurity, bedside examination with binocular indirect ophthalmoscopy has been the gold standard technique for screening, yet with several limitations. Herein, we review the current evidence that supports the role of telemedicine for the screening of infants with retinopathy of prematurity.

Purpose The tractional retinoschisis is a poorly understood, rare, and likely underappreciated entity in retinopathy of prematurity. The purpose of this article is to describe clinical findings and surgical management of tractional retinoschisis in retinopathy of prematurity, masquerading as Stage 4 retinopathy of prematurity retinal detachment. Methods A retrospective review of a single case with literature review and case discussion. Results In this report, we describe a child with retinopathy of prematurity and tractional schisis, who initially presented with vitreous hemorrhage and was effectively managed by vitrectomy and inner wall retinectomy. At 5 months after vitrectomy, the child demonstrated complete collapse of the retinoschisis with intact posterior pole and brisk light perception. Conclusion Vitrectomy with or without inner wall retinectomy is effective in the management of tractional retinoschisis.

Pars plana vitrectomy represents an important treatment tool in eyes with diabetic macular edema (DME). Vitrectomy primarily promotes resolution of DME by relieving tangential and vitreomacular traction, but has additional benefits of removing depot of VEGF and pro-inflammatory cytokines, and improving macular oxygen delivery and perfusion. Therefore, vitrectomy has most significant benefit in tractional DME, and potential efficacy in non-tractional DME. The advent of modern vitrectomy with advanced visualization techniques has made macular surgery significantly more safe and improved treatment outcomes. The purpose of the article is to review major studies on the surgical treatment of DME and offer perspectives on strategies to maximize anatomic and functional outcomes of diabetic vitrectomy.

BACKGROUND AND OBJECTIVE: Punctate inner choroidopathy (PIC) is an inflammatory chorioretinopathy characterized by multiple punctate, hypopigmented fundus lesions. Optical coherence tomography angiography (OCTA) is an emerging imaging modality that enables high-resolution visualization of the retinal and choroidal vasculature. The objective of this study is to examine the OCTA findings in PIC. PATIENTS AND METHODS: Observational, retrospective review of five patients with PIC. RESULTS: OCTA revealed several features in PIC lesions: distinctly visible choroidal neovascular membranes when present, as well as flow voids within the choroid and choriocapillaris layers that correspond with hypocyanescent lesions on indocyanine green angiography. CONCLUSION: OCTA may serve as a useful adjunctive imaging modality in diagnosing and monitoring patients with PIC. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:786–792.]

Purpose To determine surgical outcomes in patients with uveitis who underwent surgery for epiretinal membrane. Design Multicenter, interventional, retrospective, consecutive case series. Subjects Patients with a history of controlled uveitis and concurrent visually significant epiretinal membrane. Methods All eyes underwent 23-gauge pars plana vitrectomy with membrane and internal limiting membrane peeling between 2011 and 2015. Demographic data, visual acuity, slit lamp and fundoscopic examination, and optical coherence tomography were reviewed preoperatively and postoperatively. Main Outcome Measures Visual acuity, mean central foveal thickness, macular cube volume, and uveitic activity preoperatively and postoperatively at 1, 3, and 6 months. Results Fifteen patients (17 eyes) were included. The mean follow-up duration was 23.2 months. Seventeen eyes (88.2%) received intravenous methylprednisolone and 10 eyes (58.8%) received intraocular steroids at the time of surgery. There was a significant improvement in mean central foveal thickness (517 vs. 371 microns; P = 0.01) and macular cube volume (12.1 vs. 9.4 mm 3 ; P = 0.01) 6 months postoperatively. There were no epiretinal membrane recurrences. There was a trend toward improved mean postoperative visual acuity at 6 months (0.8 [±0.6] vs. 0.6 [±0.6] logarithm of the minimum angle of resolution units; P = 0.36). All eyes were inactive at the final visit, but 5 eyes (29.4%) required further immunomodulatory therapy postoperatively. One eye developed increased intraocular pressure that required topical therapy. Conclusion Eyes with a history of controlled uveitis have low surgical recurrence rates that are comparable with those without uveitis. Most patients do not require escalation of immunomodulatory therapy after surgery.

BACKGROUND AND OBJECTIVE: To characterize the in vivo microstructural features of patients with history of retinopathy of prematurity (ROP). PATIENTS AND METHODS: A single-center, retrospective imaging case series during which a chart review was performed of consecutive patients with history of ROP who underwent spectral-domain optical coherence tomography (SD-OCT) with or without enhanced depth imaging. Eyes with time-domain OCT, no light perception, or uninterpretable SD-OCT images were excluded. Main outcome measures included best-corrected visual acuity (BCVA) and exploratory SD-OCT findings. RESULTS: A total of 186 eyes of 112 patients (mean age: 31.5 years; range: 8 years to 70 years) were imaged. Mean visual acuity was 20/150 (range: 20/20 to light perception). Mean foveal thickness (MFT) and subfoveal choroidal thickness (SCT) measured 270.93 µm ± 56.40 µm and 239.87 µm ± 73.00 µm, respectively. There was a negative correlation between ROP stage and MFT (Rho = −0.19; P = .027), but not with SCT (Rho = −0.03; P = .748). There were negative correlations between BCVA and MFT (Rho = −0.23; P < .01) and SCT (Rho = −0.19; P = .04). Ellipsoid zone (EZ) abnormalities, inner retinal layer thickening, and presence of chorioretinal atrophy were associated with higher ROP stage ( P < .001) and poorer visual acuity (Rho = 0.59; P < .001). The presence of retinoschisis (n = 36/186; 19%) was associated with poorer visual acuity ( P < .001), but did not correlate with higher ROP stage ( P = .17). Epiretinal membrane-like dense hyaloidal organization and vitreoretinal interface abnormalities were seen in 69% (130/186) and 33% (63/186) of eyes, respectively, but were not associated with ROP stage ( P = .87) or visual acuity ( P = .54). After controlling for EZ abnormalities, foveal hypoplasia, macular schisis, inner retinal thickening, chorioretinal atrophy, and ROP stage, the independent risk factors for poorer visual acuity were EZ abnormalities (Beta = 0.38; P < .001), chorioretinal atrophy (Beta = 0.18; P = .03), and ROP stage (Beta = 0.22; P < .01). CONCLUSION: SD-OCT imaging identified a variety of microstructural abnormalities present in patients with history of ROP. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:1086–1094.]

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon’s capabilities.

CASE REPORT: Norrie disease is a rare, but devastating cause of pediatric retinal detachment, universally portending a poor visual prognosis. This paper describes successful surgical management of an infant with total retinal detachment associated with Norrie disease mutation. The infant was a full-term white male who presented with bilateral total funnel retinal detachments (RDs). He underwent genetic testing, which demonstrated single-point mutation 133 G>A transition in exon 2 of the NDP gene. The retinal detachment was managed with translimbal iridectomy, lensectomy, capsulectomy, and vitrectomy. Careful dissection of the retrolental membranes resulted in opening of the funnel. Single-stage surgery in this child's eye achieved re-attachment of the posterior pole with progressive reabsorption of subretinal fluid and cholesterol without the need for external drainage. Fluorescein angiography, performed at 2 months postoperatively, demonstrated perfusion of major vascular arcades, but with significant abnormalities and aneurysmal changes of higher-order vessels, suggestive of retinal and vascular dysplasia. The child has maintained brisk light perception vision. Early surgical intervention with careful dissection of tractional tissues can potentially result in good anatomic outcomes in some patients with Norrie disease-associated retinal detachment. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:260–262. ]

Bozho Todorich,1,2 Paul Hahn2 1Associated Retinal Consultants and Oakland University William Beaumont School of Medicine, Royal Oak, MI, 2Duke Eye Center, Duke University Medical Center, Durham, NC, USA Introduction: We aim to describe a mechanism of vision loss following vitrectomy surgery with retrobulbar block (RBB) associated with severe vascular stasis of the optic nerve and macula in order to improve safety of local anesthesia for ophthalmic surgery. Case presentation: We report three cases of patients who underwent pars plana vitrectomy (PPV) with retrobulbar anesthesia with no retrobulbar hemorrhage or elevated intraocular pressure (IOP). At the beginning, in each case, hypoperfusion of optic nerve and macula was noted. In the case of one patient with significant vasculopathic risk factors, the vascular stasis was severe, while in the other two cases, it was mild-to-moderate. In all cases, the perfusion of posterior pole began to improve almost immediately following the start of PPV. Because the IOP was not elevated and no retrobulbar hemorrhage was present, this suggested a compartment syndrome in the intraconal space. The patient with severe vascular stasis developed finger-counting vision but had normal postoperative angiogram findings and unrevealing cardiovascular workup. In the other two milder cases, the occurrence of ischemia was not visually significant. Conclusion: Intraoperative ischemia should be considered in all cases of unexplained vision loss after ophthalmic surgery using RBB. Attention to vasculopathic risk factors and intraoperative hemodynamic parameters, in addition to the use of parabulbar block, may avoid this complication and permanent vision loss. Keywords: macular ischemia, pars plana vitrectomy, retrobulbar block, central retinal artery occlusion

Ophthalmic surgeons manipulate micron-scale tissues using stereopsis through an operating microscope and instrument shadowing for depth perception. While ophthalmic microsurgery has benefitted from rapid advances in instrumentation and techniques, the basic principles of the stereo operating microscope have not changed since the 1930’s. Optical Coherence Tomography (OCT) has revolutionized ophthalmic imaging and is now the gold standard for preoperative and postoperative evaluation of most retinal and many corneal procedures. We and others have developed initial microscope-integrated OCT (MIOCT) systems for concurrent OCT and operating microscope imaging, but these are limited to 2D real-time imaging and require offline post-processing for 3D rendering and visualization. Our previously presented 4D MIOCT system can record and display the 3D surgical field stereoscopically through the microscope oculars using a dual-channel heads-up display (HUD) at up to 10 micron-scale volumes per second. In this work, we show that 4D MIOCT guidance improves the accuracy of depth-based microsurgical maneuvers (with statistical significance) in mock surgery trials in a wet lab environment. Additionally, 4D MIOCT was successfully performed in 38/45 (84%) posterior and 14/14 (100%) anterior eye human surgeries, and revealed previously unrecognized lesions that were invisible through the operating microscope. These lesions, such as residual and potentially damaging retinal deformation during pathologic membrane peeling, were visualized in real-time by the surgeon. Our integrated system provides an enhanced 4D surgical visualization platform that can improve current ophthalmic surgical practice and may help develop and refine future microsurgical techniques.

In a recent issue of Retina, Chang et al1 published the results of a 1-year prospective study of ranibizumab for choroidal neovascularization (CNV) associated with submacular hemorrhage (SMH) in patients with neovascular age-related macular degeneration (nAMD). This is the first prospective study re

There is a critical relationship between oligodendrocyte development, myelin production, and iron bioavailability. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding molecular mechanisms of iron import into oligodendrocytes is necessary for devising effective strategies for iron supplementation. Although transferrin has been considered as an essential component of oligodendrocyte media in culture, oligodendrocytes in vivo lack transferrin receptors. We have established that receptors for H-ferritin (HF) exist on cells of oligodendroglial lineage and that uptake of extracellular HF by oligodendrocyte progenitors is via receptor mediated endocytosis. These data strongly argue that ferritin is a major source of iron for oligodendrocytes. In this study, we demonstrate that media deficient in transferrin results in loss of viability of oligodendrocyte progenitors in culture. Cell loss could be prevented by supplementing the media with HF. Moreover, the addition of extracellular HF stimulates development of oligodendrocyte progenitor cells (OPCs) by increasing expression of myelin basic protein (MBP) and olig2 proteins without increasing their proliferation. The effect of HF on the OPCs could be mimicked by addition of membrane permeable 3,5,5-trimethylhexanoyl ferrocene (TMH-Fe) as an iron source to the media, but not membrane-impermeable ferric ammonium citrate. Overall, therefore, our results demonstrate the importance of iron for OPCs viability and differentiation and identify extracellular HF as a critical source of iron for oligodendrocytes. Given that ferritin receptors, but not transferrin receptors can be demonstrated on oligodendrocytes in vivo, the delivery of iron to oligodendrocytes viaferritin may be the more biological relevant delivery system. © 2011 Wiley-Liss, Inc.

The second post-natal week in rat is the period of the most intense oligodendrocyte development and myelination. This period coincides with peak iron import by oligodendrocytes. During that time oligodendrocyte progenitors (OPCs) are sensitive to agents that may disturb normal iron homeostasis and assimilation of iron into these cells. One mechanism by which iron homeostasis can be disrupted is by environmental exposure to other metals. Vanadium is a transition metal, and exposure to vanadium during early brain development produces hypomyelination with variety of related neuro-behavioral phenotypes. In the current study, we investigated mechanisms of hypomyelination induced by vanadium exposure in developing rat brain. We demonstrate that both in vivo and in vitro, OPCs are more sensitive to vanadium exposure than astrocytes or mature oligodendrocytes. Vanadium exposure in OPCs resulted in increased ROS generation and increased annexinV labeling suggestive of apoptosis. Because ferritin is a major iron delivery protein for oligodendrocytes, we exposed the cells to recombinant ferritin and iron both of which exacerbated vanadium cytotoxicity, while the iron chelator desferroxamine (DFO) prevented cytotoxic/apoptotic effects of vanadium. To illustrate relationship between ferritin and vanadium, we demonstrate that vanadium exacerbated DNA nicking produced by iron-rich spleen ferritin, but not iron-poor apoferritin, resulting in a single and double strand breaks in a DNA relaxation assay. We propose that developmental exposure to vanadium interferes with normal iron assimilation into oligodendrocytes resulting in oxidative stress and apoptosis. Therefore, depletion of OPCs due to vanadium exposure in early post-natal period may be an important mechanism of vanadium-induced hypomyelination.

Oligodendrocytes stain more strongly for iron than any other cell in the CNS, and they require iron for the production of myelin. For most cell types transferrin is the major iron delivery protein, yet neither transferrin receptor protein nor mRNA are detectable in mature oligodendrocytes. Thus an alternative iron delivery mechanism must exist. Given the significant long term consequences of developmental iron deficiency and the iron requirements for normal myelination, identification of the iron delivery mechanism for oligodendrocytes is important. Previously we have reported that oligodendrocytes bind H-ferritin and that H-ferritin binds to white matter tracts in vivo. Recently, T cell immunoglobulin and mucin domain-containing protein-2 (Tim-2) was shown to bind and internalize H-ferritin. In the present study we show that Tim-2 is expressed on oligodendrocytes both in vivo and in vitro. Further, the onset of saturable H-ferritin binding in CG4 oligodendrocyte cell line is accompanied by Tim-2 expression. Application of a blocking antibody to the extracellular domain of Tim-2 significantly reduces H-ferritin binding to the differentiated CG4 cells and primary oligodendrocytes. Tim-2 expression on CG4 cells is responsive to iron; decreasing with iron loading and increasing with iron chelation. Taken together, these data provide compelling evidence that Tim-2 is the H-ferritin receptor on oligodendrocytes suggesting it is the primary mechanism for iron acquisition by these cells.

Inflammatory processes play a key role in the pathogenesis of a number of common neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Abnormal iron accumulation is frequently noted in these diseases and compelling evidence exists that iron is involved in inflammatory reactions. Histochemical stains for iron repeatedly demonstrate that oligodendrocytes, under normal conditions, stain more prominently than any other cell type in the brain. Therefore, we examined the hypothesis that cytokine toxicity to oligodendrocytes is iron mediated. Oligodendrocytes in culture were exposed to interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). Toxicity was observed in a dose-dependent manner for IFN-gamma and TNF-alpha. IL-1beta was not toxic in the concentrations used in this study. The toxic concentration of IFN-gamma, and TNF-alpha was lower if the cells were iron loaded, but iron loading had no effect on the toxicity of IL-1beta. These data provide insight into the controversy regarding the toxicity of cytokines to oligodendrocytes by revealing that iron status of these cells will significantly impact the outcome of cytokine treatment. The exposure of oligodendrocytes to cytokines plus iron decreased mitochondrial membrane potential but activation of caspase 3 is limited. The antioxidant, TPPB, which targets mitochondria, protected the oligodendrocytes from the iron-mediated cytotoxicity, providing further support that mitochondrial dysfunction may underlie the iron-mediated cytokine toxicity. Therapeutic strategies involving anti-inflammatory agents have met with limited success in the treatment of demyelinating disorders. A better understanding of these agents and the contribution of cellular iron status to cytokine toxicity may help develop a more consistent intervention strategy.

Redox metals in the brain play many important roles in maintenance of cellular function. The maintenance of their homeostasis is of paramount importance to a number of diseases such as Alzheimer's disease and multiple sclerosis. Iron, copper, and zinc are metals of special interest in the pathogenesis of these disorders. This review will focus primarily on iron.

Importance The rate of endophthalmitis following dexamethasone intravitreal implant (DEX) has varied in large clinical trials. Furthermore, to our knowledge, the optimal management of eyes with endophthalmitis associated with DEX has not been established. Objective To report the incidence of culture-proven endophthalmitis in a single vitreoretinal practice over the course of 3 years and describe the clinical outcomes associated with each case of endophthalmitis. Design, Setting, and Participants All patients who received DEX between January 14, 2013, and August 31, 2016, were included in this retrospective single-center case series at a private vitreoretinal practice. The patients were identified during a search of the billing records over the period of interest. Cases of endophthalmitis associated with DEX were also identified. Exposures Treatment with DEX. Main Outcomes and Measures Development of endophthalmitis following DEX and the clinical management and outcomes of each case of endophthalmitis. Results Of the 1051 participants who collectively received 3593 injections of DEX, 4 patients developed endophthalmitis; all 4 patients were white, female, and 60 years or older (mean [SD] age, 75.6 [13] years). Two patients had culture-proven bacterial endophthalmitis after DEX monoinjections (0.06% of injections and 0.2% of patients). Three other cases of endophthalmitis developed after coinjection with bevacizumab (aggregate rate: 0.14% of injections and 0.38% of patients), of which 2 were culture positive. One patient developed endophthalmitis on 2 separate occasions. Vitrectomy was performed in 2 patients, and in 1 of these patients, the implant was removed. All 4 patients were treated with injection of intravitreous vancomycin and ceftazidime. Conclusions and Relevance These data suggest that endophthalmitis is a rare event following injection of DEX. However, given the rarity of endophthalmitis following DEX and the heterogeneity among our reported cases, it remains unclear whether the DEX endophthalmitis rate approximates that of intravitreous anti–vascular endothelial growth factor therapy. These data also suggest that vitrectomy with removal of DEX may not be necessary in all cases of DEX-associated endophthalmitis.

The purpose of this report is to describe a pediatric case of total retinal detachment (RD) with secondary glaucoma in the setting of posterior coloboma with the metaplastic retinal pigment epithelium showing abrupt transition to choroid plexus tissue.Retrospective case report.A 3-month-old patient presented with leukocoria and enlarged right eye. She was found to have a funnel RD with anterior displacement of lens-iris diaphragm and secondary glaucoma. Orbital imaging ruled out retinoblastoma, and posterior coloboma was identified. Intraocular pressures remained significantly elevated despite maximal medical therapy on glaucoma drops and transscleral cycloablation, and the eye was enucleated for comfort. Histologic analysis confirmed neovascularization of the iris, total RD, and posterior coloboma with the associated metaplastic retinal pigment epithelium showing abrupt transition to choroid plexus tissue.This is the first reported case of choroid plexus in the human eye. A close association of choroid plexus with coloboma and RD raises possibility that this tissue may have functionally contributed to pathogenesis of RD by secreting cerebrospinal fluid within subretinal space.