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This review evaluates the current surgical management options for refractory and atypical macular holes (MH) and proposes a treatment paradigm for approaching complex cases. A review of literature was performed to deliver a thorough discussion of the epidemiology and pathophysiology of MH as well as the historic evolution of surgical management strategies. With this context established, an update on recent surgical advances for management of large, chronic, and highly myopic MH is provided. New small MH may be adequately treated with pars plana vitrectomy, while those ≥300 μm should undergo internal limiting membrane (ILM) peel. For MH ≥400 μm with risk factors for failure, primary intervention should involve creation of an ILM flap and various methods of flap creation are discussed. For very large MH ≥700 μm or in refractory cases, autologous retinal transplants and other recently proposed procedures should be considered. While typical MHs enjoy high initial surgical success rates, atypical and refractory MH require additional intraoperative and postoperative considerations to maximize surgical success and optimize vision. With many techniques at the surgeon's disposal, patient selection becomes critical to improving outcomes.

Background: Multiple studies have described the utility of intraoperative spectral-domain OCT (SD-OCT) with two dimensional (2D) B-scan imaging in the management of numerous vitreoretinal disorders including macular holes, vitreomacular traction disorders, epiretinal membranes and retinal detachment. Some of these studies also described post-processing of the 2D B-scans to obtain 3D images. With the advancement of intraoperative OCT technology, live volumetric (4D, i.e. 3D over time) visualization of different anterior and posterior segment surgeries has been described in recent studies using intraoperative swept-source microscope-integrated OCT (SS-MIOCT). Our study aims to explore the potential utility of SS-MIOCT during vitrectomy for complications of proliferative diabetic retinopathy. Aim of the work: To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated OCT (SS-MIOCT) in vitrectomy for proliferative diabetic retinopathy (PDR) complications.Patient and Methods: In this prospective study, we analyzed a subgroup of cases with PDR complications that required vitrectomy and that were imaged by the research SS-MIOCT system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy (DR)-associated pathologies and reviewing the intraoperatively documented surgeon feedback.Results: Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (TRD, 16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes) and vitreous hemorrhage (2 eyes). Useful, good quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple DR pathologies could be imaged. SS-MIOCT provided surgical guidance, e.g. in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%) acceptable images were captured, but they were not useful due to high TRD elevation which was challenging for imaging.Conclusion: SS-MIOCT can provide important guidance during surgery for PDR complications through intraoperative identification of different pathologies and facilitation of intraoperative decision making.

To evaluate the feasibility and initial functional and anatomical outcomes of transplanting a full-thickness free graft of choroid and retinal pigment epithelium (RPE), along with neurosensory retina in advanced fibrosis and atrophy associated with end-stage exudative age-related macular degeneration with and without a concurrent refractory macular hole.During vitrectomy, an RPE-choroidal and neurosensory retinal free graft was harvested in nine eyes of nine patients. The RPE-choroidal and neurosensory retinal free graft was either placed subretinally (n = 5), intraretinally to cover the foveal area inside an iatrogenically induced macular hole over the RPE-choroidal graft (n = 3) or preretinally (n = 1) without a retinotomy wherein both free grafts were placed over the concurrent macular hole. Silicone oil endotamponade was used in all cases.Mean follow-up was 7 ± 5.5 months (range 3-19). The mean preoperative visual acuity was ∼count fingers (logarithm of the minimum angle of resolution = 2.11, range 2-3), which improved to ∼20/800 (logarithm of the minimum angle of resolution 1.62 ± 0.48, range 0.7-2, P = 0.04). Vision was stable in 5 eyes (55.6%) and improved in 4 eyes (44.4%). Reading ability improved in 5 eyes (55.6%). Postoperative complications were graft atrophy (n = 1), epiretinal membrane (n = 1), and dislocation of neurosensory retina-choroid-RPE free graft (n = 1).Combined autologous RPE-choroid and neurosensory retinal free graft is a potential surgical alternative in eyes with end-stage exudative age-related macular degeneration, including concurrent refractory macular hole.

Purpose To report differences in visual acuities among patients with Coats' disease who sought treatment at a tertiary care university-based practice. Design Single-center retrospective cohort study. Participants Patients with Coats' disease diagnosed clinically, angiographically, or both from 1995 through 2015. Methods Patients were divided into 2 groups based on date of presentation: decade 1 (1995–2005) and decade 2 (2006–2015). Main Outcome Measures Visual acuity (VA). Results Thirty-nine eyes of 39 patients were included with 19 eyes presenting in decade 1 and 20 eyes presenting in decade 2. Three patients demonstrated bilateral disease, but only the worse eye was included for analysis. Forty-seven percent of eyes in decade 1 demonstrated advanced stages of disease (stage 3B or worse) compared with 20% of eyes in decade 2. There was a trend for the mean initial presenting VA (±standard deviation) for decade 1 eyes to be worse (2.05±1.29 logarithm of the minimum angle of resolution [logMAR]) than for decade 2 eyes (1.45±0.99 logMAR; P = 0.1). From initial to final follow-up visit, mean VA also worsened for decade 1 eyes ( P = 0.03), but remained stable for decade 2 eyes ( P = 1.0). At the end of follow-up, there was a trend for mean VA for decade 1 eyes (2.28±1.17 logMAR) to be worse than for decade 2 eyes (1.60±1.15 logMAR; P = 0.07). Eight eyes were observed initially in decade 1 compared with 1 eye in decade 2, and only 1 of the observed eyes (in decade 2) developed painful glaucoma requiring enucleation. Decade 2 eyes had a higher average number of procedures per eye (6.5±4.9) compared with decade 1 eyes (1.4±1.7; P Conclusions The earlier presentation of disease in decade 2 suggests improvements in disease detection over time. Furthermore, there was a trend for eyes to have better final VA in this decade. This is due to a combination of factors, including earlier presentation of disease, fewer eyes being observed without treatment, and eyes, when treated, receiving a higher number of procedures.

Purpose To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated optical coherence tomography in vitrectomy for proliferative diabetic retinopathy complications. Methods In this prospective study, we analyzed a subgroup of patients with proliferative diabetic retinopathy complications who required vitrectomy and who were imaged by the research swept-source microscope-integrated optical coherence tomography system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy-associated pathologies and reviewing the intraoperatively documented surgeon feedback. Results Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy complications could be imaged. Swept-source microscope-integrated optical coherence tomography provided surgical guidance, e.g., in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%), acceptable images were captured, but they were not useful due to high tractional retinal detachment elevation which was challenging for imaging. Conclusion Swept-source microscope-integrated optical coherence tomography can provide important guidance during surgery for proliferative diabetic retinopathy complications through intraoperative identification of different complications and facilitation of intraoperative decision making.

Cerebral malaria (CM) is a significant cause of mortality and morbidity in sub-Saharan Africa, particularly among young children. Malarial retinopathy is the most specific clinical finding in CM, and fundus examination could help clinicians distinguish CM from other causes of encephalopathy in resource-poor areas. To assess clinician knowledge, practice patterns, and barriers to the use of funduscopy in the diagnosis of CM, we designed a descriptive multinational survey of clinicians in malaria endemic areas. Results of this survey showed that 19% of respondents were not aware of the utility of eye examinations for malarial retinopathy, and almost half (49%) never or almost never examine the eyes in cases of suspected CM. Educating clinicians about malarial retinopathy could be important in improving diagnostic specificity for CM.

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.

We introduce a metric in graph search and demonstrate its application for segmenting retinal optical coherence tomography (OCT) images of macular pathology. Our proposed “adjusted mean arc length” (AMAL) metric is an adaptation of the lowest mean arc length search technique for automated OCT segmentation. We compare this method to Dijkstra’s shortest path algorithm, which we utilized previously in our popular graph theory and dynamic programming segmentation technique. As an illustrative example, we show that AMAL-based length-adaptive segmentation outperforms the shortest path in delineating the retina/vitreous boundary of patients with full-thickness macular holes when compared with expert manual grading.

Background. Activation of innate immunity plays a key role in determining the outcome of an infection. Here, we investigated whether Toll-like receptors (TLRs) are involved in retinal innate response and explored the prophylactic use of TLR2 ligand in preventing bacterial endophthalmitis. Methods. C57BL/6 mice were given intravitreal injections of Pam3Cys, a synthetic ligand of TLR2, or vehicle (phosphate-buffered saline) 24 h prior to Staphylococcus aureus inoculation. The severity of endophthalmitis was graded by slit lamp, electroretinography, histological examinations, and determination of bacterial load in the retina. The expression of cytokines/chemokines and cathelicidin-related antimicrobial peptide was assessed by enzyme-linked immunosorbent assay and Western blot, respectively. Results. Intravitreal injections of Pam3Cys up-regulated TLR2 expression in the retina of C57BL/6 mice, and Pam3Cys pretreatment significantly improved the outcome of S. aureus endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinography in C57BL/6 mice. Furthermore, Pam3Cys pretreatment activated retinal microglia cells, induced the expression of cathelicidin-related antimicrobial peptide, and remarkably reduced the bacterial load. Conclusions. This is the first report that highlights the existence and role of TLR2 in retinal innate immune response to S. aureus infection and suggests that modulation of TLR activation provides a novel prophylactic approach to prevent bacterial endophthalmitis.

Importance Aflibercept-related sterile inflammation, an event that is poorly understood, has been the subject of ongoing postmarketing reports. Objective To analyze cases of aflibercept-related sterile inflammation reported to the American Society of Retina Specialists (ASRS) Therapeutic Surveillance Committee (TSC), an independent task force formed to monitor drug- and device-related safety events. Design, Setting, and Participants A retrospective review of 56 cases in 55 patients was performed of all cases of sterile inflammation after aflibercept injection that were voluntarily reported by 12 practices throughout the United States to the ASRS TSC from December 1, 2011, through February 12, 2014. Main Outcomes and Measures Cases of aflibercept-related sterile inflammation were analyzed for baseline and demographic information, presenting symptoms and findings, visual acuity changes, injection technique, and management details. Results Among 56 reported cases of sterile inflammation, mean time to onset was 3.5 days (median, 2 days; range, 0-30 days). Most cases consisted of initial loss of vision and intraocular inflammation without prominent redness, severe pain, or hypopyon. Thirty-seven cases (66%) were treated with topical corticosteroids and/or observation alone. Mean time to resolution was 28.6 days (median, 28 days; range, 4-84 days). Although final vision was overall unchanged, some patients developed permanent vision loss, which may have resulted from inflammation and/or progression of the underlying disease. Age older than 80 years was associated with worse visual outcomes. No difference in visual outcome was detected in patients with sterile inflammation undergoing topical therapy alone vs invasive procedures (vitreous biopsy and/or intravitreal antibiotic administration and/or vitrectomy). Conclusions and Relevance With the largest number of reported cases of aflibercept-related sterile inflammation to our knowledge, this analysis suggests typical findings and an often favorable prognosis of this event. Analysis of real-world, postmarketing data has limitations, and these findings should be considered as hypothesis-generating assessments rather than a definitive reflection of this event or its typical course. Distinguishing sterile inflammation and infectious endophthalmitis at the time of presentation may often be difficult, and cautious evaluation and management of these patients are warranted. The ASRS TSC encourages active postmarketing surveillance by all physicians.

PurposeTo determine the effect of anti-vascular endothelial growth factor (VEGF) therapy on choroidal thickness in eyes with diabetic macular edema (DME).DesignA retrospective, cohort analysis of 59 eyes from 59 patients with DME without prior anti-VEGF therapy.MethodsChoroidal thickness was measured using semiautomated segmentation of enhanced depth imaging optical coherence tomography images at 0.5-mm intervals from 2.5 mm nasal to 2.5 mm temporal to the fovea. Changes in choroidal thickness with and without anti-VEGF treatment over 6 months were compared. Best-corrected visual acuity and central foveal thickness were analyzed to evaluate the association of choroidal thickness with functional and anatomic outcomes.ResultsOf the 59 eyes with DME, 26 eyes were observed without treatment, whereas 33 underwent intravitreal anti-VEGF therapy (mean number of injections, 2.73) over 6 months. In untreated eyes, there was no significant change in best-corrected visual acuity (P = .098), central foveal thickness (P = .472), or choroidal thickness at all measurements along the macula (P = .057 at the fovea). In eyes treated with anti-VEGF injections, choroidal thickness decreased significantly at the fovea (246.6 to 224.8 μm; P < .001) and at 0.5 mm nasal (240.9 to 221.9 μm; P = .002) and 0.5 mm temporal (249.3 to 224.8 μm; P = .011) to the fovea. The decrease in subfoveal choroidal thickness after anti-VEGF treatment was not associated with the cumulative number of anti-VEGF injections (R(2) = 0.031; P = .327) or to changes in best-corrected visual acuity (R(2) = 0.017; P = .470) or central foveal thickness (R(2) = 0.040; P = .263).ConclusionsCentral choroidal thickness decreases after anti-VEGF therapy for DME after 6 months, but may not be associated with functional or anatomic outcomes in eyes with DME.

Massive submacular hemorrhage can cause disastrous visual complications. Prompt displacement away from the fovea is desirable in some patients. We describe a novel surgical technique involving subretinal air as a therapeutic adjuvant for massive submacular hemorrhage displacement.

A 54-year-old woman with relapsing-remitting multiple sclerosis (MS) developed visual loss in her left eye due to a macular hemorrhage 11 months after starting fingolimod. Visual acuity was 20/80 in the left eye, with a dense retinal hemorrhage involving the fovea with adjacent hard exudate and macular thickening confirmed by spectral domain optical coherence tomography. Three months after stopping fingolimod, vision in the left eye improved to 20/30 with resolution of the macular hemorrhage and exudates. Fingolimod has been associated with macular edema, but prior to this report, the authors are unaware of it causing a macular hemorrhage in a MS patient. The authors speculate that the macular hemorrhage may be due to a disruption of cellular adhesions between vascular endothelial cells that maintain the inner blood-retinal barrier.

All injections were performed with standard techniques based on survey responses. Povidone-iodine 5% was applied before injection in all cases. Thirteen of 15 eyes were administered topical anesthesia, and 2 eyes were given subconjunctival lidocaine. All eyes were injected with the Becton Dickinson (Franklin Lakes, NJ) 1-ml Luer-Lok syringe included in the aflibercept packaging. The majority of eyes were injected in the superotemporal quadrant (12 of 15 eyes) and with a 32-G needle (13 of 15 eyes), while the remainder were injected in the inferotemporal quadrant (3 of 15 eyes) and with a 30-G needle (2 of 15 eyes). These differences likely represent individual practice pattern differences and are not an implication of these techniques. Five physicians practicing in the Northeast, the Southeast, and the Southern United States reported cases of sterile inflammation. Three physicians practiced in the same retina group, and 9 of 15 cases (60%) were reported by a single retina specialist in this practice, consistent with a clustering pattern previously reported with other intravitreal therapies. 2 All cases were attributed to 5 separate drug lots, with 3 lots accounting for 13 of 15 cases. All but 1 patient experienced symptoms within 3 days. Visual acuity generally recovered to baseline levels with nearly identical mean visual acuities at baseline (0.4 logarithm of the minimum angle of resolution) and after resolution (0.32 logarithm of the minimum angle of resolution) and a mean time to resolution of 30 days. No patient lost 1 Snellen line of visual acuity. In contrast with previous reports associating sterile inflammation from other intravitreal therapies with painless loss of vision, 3 9 of these 15 aflibercept-related cases (60%) presented with pain. Redness was noted only in eyes presenting with pain and in 6 of these 9 painful cases. It is possible that aflibercept-related sterile inflammation may be associated with higher rates of pain than previously reported. Alternatively, this difference may reflect differences in the treatment cohorts. Distinguishing between infectious and sterile endophthalmitis was at the discretion of the treating physician. Although all reported cases were culture negative, some of the cases treated with intravitreal antibiotics may have represented culture-negative infectious endophthalmitis, which is associated with increased pain, and not true sterile inflammation. However, 5 of 9 cases associated with pain were treated with vitreous tap and intravitreal antibiotic injection, and the remaining 4 cases were treated with topical steroids only, suggesting that potential misclassification of these symptoms is not fully responsible for this difference. It is likely that patients presenting with more pain were biased toward an initial diagnosis of infectious endophthalmitis (treated with tap/antibiotic injection) compared with those patients managed with topical steroids alone. Small sample size, clinical variation, and the limitations of voluntary reporting preclude definitive conclusions. Subgroup analysis did not detect any variables significantly affecting visual outcome or number of days to resolution (Tables 4 and 5; available at http://www.aaojournal.org). This letter serves as a descriptive case series to better understand the clinical characteristics of a cluster of aflibercept-related sterile inflammation. The manufacturer reports that approximately 30 000 injections had been administered during the reporting period, corresponding with a sterile inflammation rate of approximately 0.05%. Although there may certainly be additional, nonreported cases resulting in a higher actual rate, this frequency lies within the range documented by pivotal, prospective trials with aflibercept and other intravitreal agents and by retrospective analyses (Tables 6 and 7; available at http://www.aaojournal.org). The manufacturer continued to closely observe without public recalls or testing, and use of aflibercept has continued without persistent reports of unexpected rates of complications. The American Society of Retina Specialists Therapeutic Surveillance Subcommittee strongly urges practitioners to actively participate in postmarket surveillance of drug- and device-associated adverse events.

Scleral buckling is a highly successful technique for the repair of rhegmatogenous retinal detachment that requires intra-operative examination of the retina and treatment of retinal breaks via indirect ophthalmoscopy. Data suggest that scleral buckling likely results in improved outcomes for many patients but is declining in popularity, perhaps because of significant advances in vitrectomy instrumentation and visualization systems. Emerging data suggest that chandelier-assisted scleral buckling is safe and has many potential advantages over traditional buckling techniques. By combining traditional scleral buckling with contemporary vitreoretinal visualization techniques, chandelier-assistance may increase the popularity of scleral buckling to treat primary rhegmatogenous retinal detachment for surgeons of the next generation, maintaining buckling as an option for appropriate patients in the future.

Aim: To determine if recombinant tissue plasminogen activator (rtPA) injected into the vitreous cavity can penetrate the retinal vessels of porcine eyes with or without vascular occlusion. Methods: Eight eyes (group I) of four pigs underwent clamping of the optic nerve flush with the globe for 90 minutes. One hour after reperfusion, one eye of each pig was injected with 75 μg of rtPA, and the fellow eye was injected with balanced salt solution (BSS). Eyes were processed for immunohistochemistry. Four additional eyes (group II) of two pigs were subjected to the same injections, but without optic nerve clamping. Results: After reperfusion, the clinical picture was similar to that of a central retinal vein occlusion. Immunoperoxidase staining showed rtPA only in the retinal veins but not the retinal arteries in all eyes injected with rtPA in both groups I and II. Those eyes also showed intense rtPA staining at the level of the internal limiting membrane (ILM). No staining was seen at the level of the ILM or inside the retinal vessels in the BSS injected eyes. Immunofluorescence staining showed intense staining at the level of the ILM, but not inside the retinal vessels in the rtPA-injected eyes. Conclusions: rtPA may penetrate the retinal veins, but not the arteries of porcine eyes with and without vascular occlusion. The ILM may play a part in preventing rtPA penetration.

Objective To assess the safety and efficacy of combined cataract extraction, posterior chamber intraocular lens placement, pars plana vitrectomy, fluocinolone acetonide intravitreal implant (Retisert), and Ahmed valves with pars plana tube (CPR-PT) in eyes with chronic, posterior, noninfectious uveitis. Methods Retrospective study of patients who underwent CPR-PT. Outcome measures included visual acuity, intraocular pressure, inflammation, and complications. Results Eight eyes were included, with a mean follow-up of 18 months. Mean visual acuity improved from 1.89 to 0.14 logMAR (Snellen, counting fingers at 2 ft [0.6 m]) to 20/30; P = .01). Mean intraocular pressure remained stable at 16 to 17 mm Hg (P = .35). The number of glaucoma medications per eye decreased from 2.9 to 0.25 (P = .01). Systemic prednisone therapy was discontinued in all patients by 9 months postoperatively. Inflammation was well controlled in all eyes. Conclusion The CPR-PT procedure allows rapid visual rehabilitation without major short-term complications.