Use of physician extenders in ophthalmology: pros.

PURPOSE OF REVIEW: The goal of this review is to provide a description of the potential role of physician extenders within ophthalmology with a specific focus on the retina field. RECENT FINDINGS: In this editorial, the evolving role of physician extenders (e.g. physician assistants, nurse practitioners) in medicine and ophthalmology is discussed. Within ophthalmology, an experiential discussion is provided regarding the opportunities to utilize physician extenders to expand the bandwidth of subspecialists and increase access for patient care. SUMMARY: Physician extenders, such as physician assistants, provide a unique opportunity for ophthalmology to innovate next-generation care delivery models. The roles for physician extenders throughout highly specialized fields in medicine have become a critical component for team-based patient care. Within retina and other ophthalmic subspecialties, physician extenders can enable top-of-license practice for physicians, while directly expanding the umbrella of care the specialist can provide through the physician extender's role in chronic disease medical management. The deployment of a physician assistants within the retina care team provided greater access for patients requiring ongoing medical monitoring and triage for acute issues, while expanding the retina specialist's ability to see a higher volume of higher acuity patients and those patients requiring procedural/surgical interventions. Importantly, the physician assistant's role is focused exclusively on medical management of retinal diseases with all procedures being performed by the retina specialist.

Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.

LONGITUDINAL ELLIPSOID ZONE AND OUTER RETINAL INTEGRITY DYNAMICS AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To quantify ellipsoid zone (EZ) changes in integrity after epiretinal membrane (ERM) surgery, correlate findings to visual acuity, and determine predictors for prognosis. METHODS: A post hoc analysis of eyes undergoing ERM surgery pooled from the prospective DISCOVER intraoperative optical coherence tomography study and eyes undergoing conventional ERM surgery without intraoperative optical coherence tomography. Quantitative EZ features were extracted using a multilayer machine learning enabled automated segmentation platform after image analyst review/correction for segmentation accuracy. Visual acuity and EZ integrity were quantitatively assessed and correlated before and after ERM surgery. Multiple linear regression was performed to assess preoperative visual acuity and EZ features as predictors for improvement in visual acuity or EZ integrity. RESULTS: There were 177 eyes from 177 subjects that underwent ERM surgery from the DISCOVER and conventional arms. Improvement in visual acuity and multiple EZ integrity features was noted after ERM surgery, including EZ partial attenuation and EZ-retinal pigment epithelium (RPE) volume (P < 0.05). A reduction in EZ partial attenuation and increase in EZ-RPE central subfield thickness (EZ-RPE CST) was significantly correlated with improved visual acuity after ERM surgery (P < 0.05). More robust EZ-RPE CST at baseline predicted visual acuity improvement after ERM peel in regression modeling (ß = 0.005, P < 0.05). CONCLUSIONS: Longitudinal assessment of EZ features demonstrates significant postoperative improvement in multiple EZ integrity metrics after ERM surgery. Improving EZ integrity was correlated to improving the visual acuity. Ellipsoid zone integrity and visual acuity were significant predictors in regression modeling and may have value in clinical prognostication.

LONGITUDINAL ELLIPSOID ZONE DYNAMICS AFTER MACULAR HOLE REPAIR IN THE DISCOVER STUDY: Structure-Function Assessment.

PURPOSE: To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair. METHODS: This was a post-hoc analysis of eyes in the DISCOVER study undergoing vitrectomy repair for MH. Anatomical and functional data were collected through one year postoperatively. An automated retinal layer segmentation platform was used for the assessment of outer retinal metrics and volumetric reconstruction of MH. Association of longitudinal ellipsoid zone features and baseline MH height, width, and volume with VA outcomes were investigated. RESULTS: Eighty-four eyes with MH were included. The mean baseline VA was 20 of 114 and increased to 20 of 45 (P < 0.001) at postoperative Month 12 (N = 45). Successful MH closure was achieved in 98.8% of cases. Ellipsoid zone integrity metrics significantly improved from baseline (P = 0.002) and postoperative Month 1 (P < 0.001) to post-operative Month 12. Ellipsoid zone metrics independently correlated with VA at all follow-up visits (P < 0.05). Increased baseline MH width and volume negatively correlated with the VA at postoperative Month 12 (P < 0.001). Preoperative VA and EZ integrity on optical coherence tomography were predictors for postoperative VA. CONCLUSION: Baseline MH volumetric parameters and EZ parameters were associated with VA outcomes after repair.

RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY.

PURPOSE: Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. METHODS: Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated. RESULTS: Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34). CONCLUSION: Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing. TRIAL REGISTRATION: RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.

Safety and Efficacy of Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of anti-vascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (AMD). METHODS: A literature search of the PubMed and Cochrane Library databases was last conducted in February 2017; there were no date restrictions, and the search was limited to studies published in English. The combined searches yielded 191 citations, 28 of which were selected because they were clinical trials and were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous Panel to review in full. The panel methodologist then assigned a level of evidence rating to each study. RESULTS: Sixteen of the 28 citations provided level I evidence supporting the use of anti-VEGF agents for neovascular AMD, including intravitreal ranibizumab, aflibercept, and bevacizumab. Eight studies reviewed provided level II evidence, and 4 studies provided level III evidence, but only the level I studies are included in this assessment. There are long-term follow-up data on the efficacy of ranibizumab and bevacizumab (≥5 years), but these data are subject to the bias of incomplete follow-up. CONCLUSIONS: Review of the literature indicates that intravitreal injection of anti-VEGF therapy is safe and effective for neovascular AMD over 2 years, the period for which data are available. Further research is needed to evaluate the long-term safety and comparative efficacy of these agents.

Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count.

PURPOSE: To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. DESIGN: Retrospective image analysis study. METHODS: Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. MAIN OUTCOME MEASURES: Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. RESULTS: Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10-16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10-16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10-7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. CONCLUSIONS: Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

The DISCOVER Study 3-Year Results: Feasibility and Usefulness of Microscope-Integrated Intraoperative OCT during Ophthalmic Surgery.

PURPOSE: To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. DESIGN: Prospective, consecutive case series. PARTICIPANTS: Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. METHODS: The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. MAIN OUTCOME MEASURES: Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. RESULTS: Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%-98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%-49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%-33.0%). CONCLUSIONS: The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

THE INTEGRATIVE SURGICAL THEATER: Combining Intraoperative Optical Coherence Tomography and 3D Digital Visualization for Vitreoretinal Surgery in the DISCOVER Study.

PURPOSE: To evaluate the feasibility of integrating intraoperative optical coherence tomography (OCT) with a digital visualization platform for vitreoretinal surgery. METHODS: The DISCOVER study is a prospective study examining microscope-integrated intraoperative OCT across multiple prototypes and platforms. For this assessment, a microscope-integrated OCT platform was combined with a three-dimensional (3D) surgical visualization system to allow for digital display of the OCT data stream on the large immersive display. Intraoperative OCT scans were obtained at various surgical milestones that were directly overlaid to the surgical view in a 55-inch passive 3D 4K high-definition display. Surgeon feedback was obtained related to system performance and integration into the surgical procedures through a prespecified surgeon questionnaire. RESULTS: Seven eyes of seven subjects were identified. Clinical diagnosis included epiretinal membrane (n = 3), macular hole (2), symptomatic vitreous opacity (1), and proliferative vitreoretinopathy (1). Optical coherence tomography images were successfully obtained and displayed on the 4K screen in all cases. Intraoperative OCT images facilitated identification of subtle retinal alterations. Surgeons reported that the 4K screen seemed to provide improved visualization of the OCT data stream compared with the semitransparent ocular view. Surgeons were able to examine the OCT data on the 4K screen without reverting to the external display system of the microscope. The system provided a uniform surgical visualization experience for both the surgeon and the assistant. In addition, the digital platform allowed all surgical personnel to simultaneously view both the OCT and the surgical field. All eyes underwent uneventful vitrectomy without reverting to the conventional microscope. No intraoperative adverse events occurred. CONCLUSION: Integration of OCT into the digital visualization system may enable unique opportunities for surgeon feedback of intraoperative diagnostics. The overlay of the OCT data onto the 4K monitor seemed to provide excellent visualization of OCT details. Further research is needed to compare the conventional microscope-based approach to the digital 3D screen approach in regards to intraoperative OCT.

ELLIPSOID ZONE MAPPING AND OUTER RETINAL ASSESSMENT IN STARGARDT DISEASE.

PURPOSE: To quantify and correlate ellipsoid zone and photoreceptor outer segment changes with visual acuity in Stargardt disease. METHODS: An institutional review board-approved study of 32 eyes with Stargardt disease was performed. After spectral domain optical coherence tomography, the macular cube was exported into a novel analysis tool and volumetric assessment from the ellipsoid zone to the retinal pigment epithelium was performed. Using this information, mapping was completed with en face representation of the height between the ellipsoid zone and retinal pigment epithelium. This analysis provided quantification of ellipsoid zone and photoreceptor outer segments, including atrophy (ellipsoid zone to retinal pigment epithelium thickness = 0 µm) and attenuation (ellipsoid zone to retinal pigment epithelium thickness <20 µm). These parameters were compared with visual acuity and controls (n = 12 eyes). RESULTS: Visual acuity ranged from 20/30 to 20/250. The central foveal B-scan area of ellipsoid and photoreceptor outer segments was significantly less than controls (0.13 ± 0.05 mm vs. 0.17 ± 0.03 mm, respectively, P = 0.0074). The central foveal B-scan mean thickness measured 22.52 ± 9.0 µm in Stargardt versus 30.0 ± 5.08 µm (P = 0.0096). Atrophy and attenuation were significantly higher in Stargardt patients (22% vs. 1%, P = 0.005 and 43% vs. 1%, P = 0.0002). Visual acuity directly correlated with ellipsoid zone/outer segment volume (R = 0.57, P < 0.005) and inversely correlated with attenuation and atrophy (R = -0.53 and -0.57; P < 0.005 for all). CONCLUSION: Eyes with Stargardt disease frequently have significant disruption of the ellipsoid zone and outer segments. This degenerative change was successfully quantified with a novel assessment platform and identified correlates with visual function. This software provides the opportunity for quantitative assessment and possible longitudinal surveillance.

FACTORS ASSOCIATED WITH DEVELOPMENT OF DISSOCIATED OPTIC NERVE FIBER LAYER APPEARANCE IN THE PIONEER INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY STUDY.

PURPOSE: To assess the relationship of dissociated optic nerve fiber layer (DONFL) and intraoperative membrane-peeling dynamics as visualized using intraoperative optical coherence tomography (OCT), and to evaluate the functional implications of DONFL. METHODS: This was a post hoc analysis of eyes undergoing membrane peeling for vitreomacular interface disorders in the prospective PIONEER intraoperative OCT study. Retinal layer measurements in preincision and postpeel intraoperative OCT images were obtained. The primary outcome was development of DONFL appearance on spectral domain OCT at 6-month follow-up. Secondary outcomes included correlation of DONFL with surgical technique, surgical indication, intraoperative OCT findings, and retinal sensitivity. RESULTS: Ninety-five eyes were included. The prevalence of DONFL at 6 months was 36%. Increased inner retinal layer thickness on intraoperative OCT immediately after membrane peeling was associated with development of DONFL (P < 0.01). Macular hole repair was significantly associated with DONFL appearance. Peel technique (forceps vs. diamond-dusted membrane scraper) was not associated with DONFL. There was no difference in retinal sensitivity or visual acuity between eyes with or without DONFL. CONCLUSION: Acute postpeel increase in inner retinal thickness and macular hole repair were associated with development of DONFL appearance. However, it is unclear whether the surgical indication (e.g., macular hole) or the surgical manipulations performed (e.g., internal limiting membrane peeling) is the major factor that has an impact on DONFL appearance. Overall, these findings suggest that one mechanism in the development of DONFL appearance may be intraoperative trauma to the inner retina, potentially during internal limiting membrane peeling (e.g., macular hole repair).

Therapies for Macular Edema Associated with Branch Retinal Vein Occlusion: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the available evidence on the ocular safety and efficacy of current therapeutic alternatives for the management of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: Literature searches were last conducted on January 31, 2017, in PubMed with no date restrictions and limited to articles published in English, and in the Cochrane Database without language limitations. The searches yielded 321 citations, of which 109 were reviewed in full text and 27 were deemed appropriate for inclusion in this assessment. The panel methodologist assigned ratings to the selected studies according to the level of evidence. RESULTS: Level I evidence was identified in 10 articles that addressed anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME, including intravitreal bevacizumab (5), aflibercept (2), and ranibizumab (4). Level I evidence was identified in 6 studies that examined intravitreal corticosteroids, including triamcinolone (4) and the dexamethasone implant (2). Level I evidence also was available for the role of macular grid laser photocoagulation (7) and scatter peripheral laser surgery (1). The inclusion of level II and level III studies was limited given the preponderance of level I studies. The number of studies on combination therapy is limited. CONCLUSIONS: Current level I evidence suggests that intravitreal pharmacotherapy with anti-VEGF agents is effective and safe for ME secondary to BRVO. Prolonged delay in treatment is associated with less improvement in visual acuity (VA). Level I evidence also indicates that intravitreal corticosteroids are effective and safe for the management of ME associated with BRVO; however, corticosteroids are associated with increased potential ocular side effects (e.g., elevated intraocular pressure, cataracts). Laser photocoagulation remains a safe and effective therapy, but VA results lag behind the results for anti-VEGF therapies.

Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN). METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective. RESULTS: Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear. CONCLUSIONS: Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.

The Impact of Systemic Factors on Clinical Response to Ranibizumab for Diabetic Macular Edema.

PURPOSE: To evaluate the effect of systemic factors on best-corrected visual acuity (BCVA) achieved with ranibizumab (Lucentis; Genentech, Inc, South San Francisco, CA) for treatment of diabetic macular edema (DME) in the RIDE and RISE phase 3 studies. DESIGN: Exploratory, post hoc analysis of 2 randomized, double-masked, sham-injection controlled studies. PARTICIPANTS: Adults with DME, BCVA of 20/40 to 20/320 Snellen equivalent, and central foveal thickness of 275 µm or more. METHODS: Analysis of RIDE (clinicaltrials.gov identifier, NCT00473382) and RISE (clinicaltrials.gov identifier, NCT00473330) pooled ranibizumab data through month 24. Change in BCVA was assessed for association with the following covariates: age, body mass index (BMI), blood pressure, serum glucose, glycosylated hemoglobin (HbA1c), blood urea nitrogen, serum creatinine, estimated glomerular filtration rate, and blood chemistry variables. Change in BCVA at month 24 was assessed according to the following categories of diabetes medication use history: insulin only (n = 193), insulin plus other medications (n = 221), or other noninsulin medications (n = 331). MAIN OUTCOME MEASURES: Change in BCVA from baseline assessed by randomized treatment group in pooled 0.3- and 0.5-mg monthly ranibizumab groups. RESULTS: In patients with DME, vision improvement with ranibizumab was not influenced by systemic factors such as diabetes medication history, serum glucose, HbA1c, renal function, BMI, and blood pressure. Patients taking insulin with or without other medications at baseline had longer diabetes disease duration (mean, 17.4 and 20.9 years, respectively) compared with those taking other noninsulin medications (mean, 11.9 years). At month 24, among ranibizumab-treated patients, the mean BCVA change from baseline (Early Treatment Diabetic Retinopathy Study letters ± standard deviation) was not different between patients taking only insulin (12.6±11.2 letters), insulin plus other medications (12.2±12.4 letters), or other noninsulin medications (14.0±13.7 letters). Mean BCVA change also was comparable among patients taking thiazolidinediones (12.9±9.7 letters) and those not taking thiazolidinediones (13.2±13.3 letters). CONCLUSIONS: There were no associations between systemic factors (baseline values or change from baseline) and mean change of BCVA at month 24. These results suggest that visual response to ranibizumab therapy in DME was not influenced by nonocular factors related to systemic management of diabetes in the RIDE and RISE studies.

Clinical utility of intraoperative optical coherence tomography.

PURPOSE OF REVIEW: To explore the clinical utility of intraoperative optical coherence tomography (iOCT) for the management of vitreoretinal conditions. RECENT FINDINGS: The role of iOCT in guiding surgical decision-making and surgical manipulations during vitreoretinal procedures has been evaluated by multiple studies. This imaging modality is emerging as a valuable asset during procedures for vitreoretinal interface disorders, retinal detachments, submacular surgeries and therapeutics, and in pediatric conditions such as retinopathy of prematurity. iOCT allows the surgeon to assess completion of surgical goals and to directly monitor the architectural impact of instrument-tissue interactions that may correlate with eventual prognosis. The technology has gone through numerous iterations with the eventual goal being the development of a user-friendly, efficient, and integrated system that provides surgeons with 'real-time' feedback during ophthalmic surgeries to allow for a comprehensive image-assisted vitreoretinal surgery platform. SUMMARY: The role of iOCT in ophthalmic surgery has been evolving with the help of ongoing research to define its utility in the operating room and to develop integrative technologies. Advancements in OCT-friendly surgical instrumentation and in integrative capabilities of this technology may help achieve more widespread adoption of this technology in the vitreoretinal surgical theater. Although the evidence appears clear that this technology impacts surgical decision-making, additional research is needed. However, further research is needed to determine the influence of this technology on overall patient outcomes.

ELLIPSOID ZONE MAPPING AND OUTER RETINAL CHARACTERIZATION AFTER INTRAVITREAL OCRIPLASMIN.

PURPOSE: To assess outer retinal architectural alterations after intravitreal ocriplasmin with a novel automated ellipsoid zone (EZ) mapping algorithm. METHODS: A single-center, retrospective, consecutive case series of image analysis was performed. Quantitative assessment of EZ status imaged with spectral-domain optical coherence tomography was performed before and after single intravitreal injection of 0.125 mg of ocriplasmin (Jetrea, Thrombogenics). A novel EZ mapping algorithm was used to assess the EZ retinal pigment epithelium (RPE) central area, EZ-RPE macular volume, and en face EZ integrity based on the percentage of sampling areas with 20 µm or greater EZ-RPE thickness. Longitudinal assessment of these changes with custom optical coherence tomography reading software was completed. Clinical characteristics and outcomes were compared with these retinal changes. RESULTS: Nineteen eyes were included in this study. The retinal volume between EZ and RPE was significantly reduced at 1 week after ocriplasmin (P = 0.0036). Seven of 19 patients (36.8%) complained of color abnormalities or brightness reduction after injection. All of these seven patients had increased subretinal fluid after ocriplasmin and EZ attenuation. The EZ-RPE volume was reduced at 1 week (P = 0.0036), 1 month (P = 0.015) after ocriplasmin, and restored by 3 months. The area with EZ-RPE thickness below 20 µm was increased at 1 week (P = 0.046) after ocriplasmin and recovered with time. CONCLUSION: Mapping of EZ is feasible to assess EZ-RPE volume and overall EZ integrity with en face thickness mapping. Alterations in EZ occur in a significant proportion of eyes after ocriplasmin therapy. The EZ-RPE volume and the EZ-RPE central foveal area typically recover to baseline by 3 months. This effect appears to be panretinal and associated with subjective symptoms.

VOLUMETRIC SINGLE-LAYER INNER RETINAL ANALYSIS IN PATIENTS WITH HYDROXYCHLOROQUINE TOXICITY.

PURPOSE: To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes. METHODS: Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients. RESULTS: There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P < 0.001), and outer plexiform layer to retinal pigment epithelium (P < 0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P > 0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02). CONCLUSION: Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity.

Globe Loss From Intraocular Invasion of MIRAgel Scleral Buckle Components.

PURPOSE: To describe intraocular invasion of MIRAgel scleral buckles requiring evisceration. METHODS: This is an Institutional Review Board-approved retrospective consecutive case series of eyes requiring evisceration secondary to intraocular intrusion of MIRAgel implants performed at the Cole Eye Institute from 2000 to 2014. Charts were reviewed for age at surgery, gender, laterality, time between MIRAgel placement and evisceration, preoperative examination and imaging results, intraoperative findings, postoperative complications, and duration of follow up. RESULTS: Five eyes of 5 patients underwent evisceration due to a blind, painful eye secondary to MIRAgel expansion. The mean time between MIRAgel placement and evisceration was 21 years (range: 17-30 years). Preoperative ultrasound identified intraocular MIRAgel in 3 of 5 cases; however, intraocular MIRAgel was identified during surgery in all 5 cases. A transocular-approach orbitotomy was performed at the time of evisceration in an effort to remove the MIRAgel. Postoperative complications included ptosis and inability to retain an ocular prosthesis. No cases of orbital implant extrusion occurred. CONCLUSION: Scleral invasion and intraocular penetration of MIRAgel may occur decades after placement. This may result in a blind, painful eye requiring evisceration and orbitotomy to remove residual material. Suspicion of intraocular penetration of implant should be high in blind, painful eyes. Surgical removal can be difficult due to MIRAgel fragmentation. Conjunctival insufficiency may result in the need for further surgery after evisceration.

Topical Nonsteroidal Anti-inflammatory Drugs and Cataract Surgery: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To review the available evidence on the effectiveness of prophylactic topical nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing vision loss resulting from cystoid macular edema (CME) after cataract surgery. METHODS: Literature searches of the PubMed and the Cochrane Library databases were last conducted on January 21, 2015, with no date restrictions. The searches retrieved 149 unique citations. The first author reviewed the abstracts of these articles and selected 27 articles of possible clinical relevance for full-text review. Of these 27 articles, 12 were deemed relevant to analyze in full. Two additional articles were identified from the reference list of the selected articles, and another article was identified from a national meeting. The panel methodologist assigned ratings of level of evidence to each of the selected citations. RESULTS: Nonsteroidal anti-inflammatory drug therapy was effective in reducing CME detected by angiography or optical coherence tomography (OCT) and may increase the speed of visual recovery after surgery when compared directly with placebo or topical corticosteroid formulations with limited intraocular penetration. However, the use of NSAIDs did not alter long-term (≥3 months) visual outcomes. Furthermore, there was no evidence that the benefits observed with NSAID therapy could not be obtained similarly with equivalent dosing of a corticosteroid. The reported impression that there is a pharmacologic drug synergy from the use of both an NSAID and a corticosteroid is not supported by the literature. There is no uniform method of reporting CME in the literature, which prevents accurate assessment of its incidence and response to anti-inflammatory therapies. CONCLUSIONS: Cystoid macular edema after cataract surgery has a tendency to resolve spontaneously. There is a lack of level I evidence that supports the long-term benefit of NSAID therapy to prevent vision loss from CME at 3 months or more after cataract surgery. Although dosing of NSAIDs before surgery may hasten the speed of visual recovery in the first several weeks after cataract surgery, there is no evidence that this practice affects long-term visual outcomes. Standardized reporting of CME based on OCT may allow for more uniform quantitation of its incidence and more reliable assessment of treatment outcomes.

Therapies for macular edema associated with central retinal vein occlusion: a report by the American Academy of Ophthalmology.

PURPOSE: To review the available evidence regarding the safety and efficacy of therapies for the treatment of macular edema (ME) associated with central retinal vein occlusion (CRVO). METHODS: A literature search of the PubMed database was last conducted in March 2014 with no date restrictions but limited to articles published in English. A literature search of the Cochrane Library was also conducted in March 2014 with no date restrictions and without a language limitation. The combined searches yielded 108 citations, of which 20 were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous panel to review in full text. Three additional studies were also identified for panel review. The level of evidence of these selected studies was reviewed by the panel methodologist. RESULTS: There were 7 citations representing 4 clinical trials that provided level I evidence supporting the use of anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME associated with CRVO, including intravitreal ranibizumab (2), aflibercept (3), and bevacizumab (2). There were 3 citations representing 2 studies with level I evidence for intravitreal corticosteroid injection with dexamethasone intravitreal implant (2 citations) or triamcinolone (1 citation), although cataract and glaucoma were observed in these studies. Level I evidence is available on the limited benefit of macular grid-pattern laser photocoagulation (1 citation). Eight other citations reviewed were rated as level II, and 4 citations were rated as level III. Long-term efficacy results (≥2 years of follow-up) are limited to intravitreal ranibizumab at this time, and few studies have evaluated combination therapy with anti-VEGF and corticosteroid versus monotherapy of either class of drug. CONCLUSIONS: Level I evidence indicates that intravitreal anti-VEGF pharmacotherapy is safe and effective over 2 years for ME associated with CRVO and that delay in treatment is associated with worse visual outcomes. In addition, level I evidence demonstrates short-term efficacy of intravitreal corticosteroid but also an association with a higher frequency of adverse events.