Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy.

PURPOSE: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023. METHODS: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race. MAIN OUTCOME MEASURES: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort. RESULTS: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16). CONCLUSIONS: A dermatologic history of KHF may be a risk factor for PVR after RD repair. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

0.18 MG FLUOCINOLONE ACETONIDE INSERT FOR THE TREATMENT OF CHRONIC POSTOPERATIVE PSEUDOPHAKIC CYSTOID MACULAR EDEMA.

PURPOSE: To report the outcomes of the 0.18 mg fluocinolone acetonide insert (FAi) in the treatment of chronic (>6 months) postoperative cystoid macular edema after cataract surgery. METHODS: This was a retrospective consecutive case series of eyes with chronic postoperative cystoid macular edema treated with the FAi. Visual acuity, intraocular pressure, optical coherence tomography metrics, and supplemental therapies were extracted from the charts before and at 3, 6, 12, 18, and 21 months after FAi placement, when available. RESULTS: Nineteen eyes of 13 patients with chronic postoperative cystoid macular edema after cataract surgery underwent FAi placement with an average follow-up of 15.4 months. Ten eyes (52.6%) had a ≥2-line gain in visual acuity. Sixteen eyes (84.2%) had a ≥20% reduction in optical coherence tomography central subfield thickness. Eight eyes (42.1%) had complete resolution of CME. Improvements in central subfield thickness and visual acuity were sustained throughout individual follow-up. Compared with 18 eyes (94.7%) requiring local corticosteroid supplementation before FAi, only six eyes (31.6%) required supplementation after FAi. Similarly, of the 12 eyes (63.2%) that were on corticosteroid drops before FAi, only 3 (15.8%) required drops after FAi. CONCLUSION: Eyes with chronic postoperative cystoid macular edema after cataract surgery treated with the FAi had improved and sustained visual acuity and optical coherence tomography metrics, along with a reduction in supplemental treatment burden.

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.

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.

PURPOSE: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). PARTICIPANTS: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). METHODS: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group. MAIN OUTCOME MEASURES: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset. RESULTS: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%. CONCLUSIONS: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.

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.

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.

Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):: The Phase 2 SATURN Study.

PURPOSE: To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). DESIGN: Randomized, double-masked, placebo-controlled, phase 2 study. PARTICIPANTS: Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. METHODS: Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. RESULTS: At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 µm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 µm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] µm (P = 0.1317) in the subgroup of eyes with CST ≥300 µm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). CONCLUSIONS: Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation.

A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3-5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4-1.5 fold compared to control medium on days 3-5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.

Introduction to hypersonic vitrectomy.

PURPOSE OF REVIEW: To review the development of hypersonic vitrectomy and present the first case series in the United States. RECENT FINDINGS: From 27 September 2017 to 4 December 2017, 64 patients underwent hypersonic vitrectomy with 20 patients having conventional 23-ga vitrectomy for comparison. The preoperative diagnoses ranged from vitreous opacities to rhegmatogenous retinal detachments. The results will be presented, as well as a postoperative questionnaire on the utility of hypersonic vitrectomy in a 5-center 71-patient series. SUMMARY: With the first major innovation in vitrectomy technology since the early days of pneumatic guillotine cutters, hypersonic vitrectomy has been shown to be an efficient, effective and safe alternative.

Vibrational spectra of Pb2Bi2Te3, PbBi2Te4, and PbBi4Te7 topological insulators: temperature-dependent Raman and theoretical insights from DFT simulations.

Herein, using Raman spectroscopy, we have presented the investigation of a temperature-dependent frequency shift and the line broadening of phonon modes by inserting the atomic layers of Pb and PbTe in the prototype 3D topological insulator Bi2Te3. Good quality single crystals of Pb2Bi2Te3, PbBi2Te4, and PbBi4Te7 were grown using the modified Bridgman technique. The Raman modes show progressive blue-shift with the decrease in temperature from 298 K to 93 K in Pb2Bi2Te3, PbBi2Te4, and PbBi4Te7 due to the anharmonic vibrations of the lattice as well as the increase in the strength of Bi-Te covalent interactions. The experimental results were complemented by extensive first principles calculations, where a reasonable matching between the experimental and computational data was found. Chemical pressure, induced by the insertion of Pb and PbTe layers in Bi2Te3, modified the interactions at the boundaries of the quintuple-layers, which was evident from the evolution of the A21u mode. The enhancement in the out-of-plane Bi-Te vibrations with respect to the in-plane Bi-Te vibrations was observed at low temperatures. The temperature coefficients of the Raman modes were useful in determining the thermal conductivity, which is a key design parameter for the fabrication of spintronic devices using topological insulators. The estimated first order temperature coefficient (χ') for Pb2Bi2Te3 signified the decrease in the thermal conductivity relative to Bi2Te3, which was caused by the insertion of the Pb layers in the van der Waals gaps of Bi2Te3.

ULTRA-WIDEFIELD MULTIMODAL IMAGING OF PRIMARY VITREORETINAL LYMPHOMA.

PURPOSE: To determine the features of primary vitreoretinal lymphoma on multimodal ultra-widefield imaging and correlate these findings to clinical outcomes. METHODS: We report a retrospective, observational case series of 43 eyes of 23 patients with biopsy-proven B-cell primary vitreoretinal lymphoma. Fundus photography, fluorescein angiography (FA), optical coherence tomography, fundus autofluorescence, and indocyanine green angiography images were reviewed. Medical records were assessed for the central nervous system involvement and visual acuity outcomes at 6 and 12 months after presentation. RESULTS: Common fundus photography findings were sub-retinal pigment epithelium lesions and vitritis alone. Common ultra-widefield FA findings were vascular leakage and scleral staining. Retinal optical coherence tomography features overlying sub-retinal pigment epithelium lesions or within the macula predicted fluorescence patterns. The presence of retinal fluid or disorganization associated with hyperfluorescence and late leakage. Normal retinal structures associated with hypofluorescence of sub-retinal pigment epithelium lesions or macular leopard spotting on FA and fundus autofluorescence. Peripheral abnormalities noted on ultra-widefield fundus photography, FA, and indocyanine green angiography were more frequent than posterior pole abnormalities. No imaging characteristics predicted time to the central nervous system progression. CONCLUSION: Ultra-widefield imaging was more informative than posterior pole imaging in fundus photography, FA, and indocyanine green angiography. Common findings on multimodal ultra-widefield imaging may lead to early diagnostic vitrectomy and may reduce the delay in primary vitreoretinal lymphoma diagnosis.

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.

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).

PERIPHERAL RETINOSCHISIS IN INTERMEDIATE UVEITIS.

PURPOSE: To examine cases of intermediate uveitis complicated by retinoschisis and review the pathogenetic hypothesis. METHODS: A retrospective chart review of patients with intermediate uveitis. Data were collected at three uveitis referral centers on sex, age, best-corrected visual acuity, degree of vitritis, extent and location of snowbanking, presence of hard exudates, neovascularization, vitreous hemorrhage, and extent and nature of retinal elevations. RESULTS: A series of 23 eyes of 20 patients were examined; patient's age ranged from 10 years to 70 years and follow-up period from 8 months to 6 years. Twenty-two eyes had retinoschisis (95.6%), and 1 had retinoschisis associated with serous retinal detachment (4.3%). Extensive inferior pars plana exudates with snowbanking were present in 12 eyes (52.2%), whereas 3 eyes had inferior snowballs over the elevated retina. Neovascularization of the vitreous base accompanied by vitreous hemorrhage occurred in one eye. There was no coexisting macular pathology in 16 eyes, whereas 4 eyes had cystoid macular edema. CONCLUSION: The appearance of peripheral retinoschisis in this series of uncontrolled intermediate uveitis patients seems to be secondary to a complex balance between the persistent fluorescein leakage, a subclinical peripheral ischemia, and the constant low-grade vitreous inflammation that causes vitreous shrinkage and traction. The results of this study suggest that the absence of macroscopic changes in the retina does not preclude ischemic peripheral abnormalities, and the detection of a peripheral retinoschisis in an intermediate uveitis patient with active fluorescein leakage must suggest the need for a more aggressive form of treatment despite the good visual acuity.

RESOLUTION OF NONINFECTIOUS UVEITIC CYSTOID MACULAR EDEMA WITH TOPICAL DIFLUPREDNATE.

PURPOSE: To evaluate the short-term safety and efficacy of topical difluprednate (0.05%) for the treatment of noninfectious uveitic cystoid macular edema. METHODS: Twenty-seven patients (35 eyes) undergoing treatment with difluprednate 4 times daily for 3 weeks for noninfectious uveitic cystoid macular edema were reviewed for visual acuity, intraocular pressure, optical coherence tomography, and fluorescein angiography results. A mixed model analysis was fit with each measure as the outcome, visit as the primary predictor, and patient and eye as random effects. RESULTS: Mean central foveal thickness decreased by 117 µm (P < 0.001) at 30 ± 15 days, 124 µm (P < 0.001) at 60 ± 15 days, and 152 µm (P < 0.001) at 180 ± 30 days. Complete resolution of intraretinal fluid was observed in 15 of 34 (44%) eyes at 30 ± 15 days, 11 of 21 (52%) eyes at 60 ± 15 days, and 9 of 12 (75%) eyes at 180 ± 30 days. Improvement in fluorescein leakage was noted in 7 of 8 eyes (88%). Visual acuity improved by a mean of 5 letters (P = 0.001) at 30 ± 15 days, 5.5 letters (P = 0.007) at 60 ± 15 days, and 7 letters (P = 0.032) at 180 ± 30 days. Mean increase in intraocular pressure was 1.48 mmHg at 30 ± 15 days (P = 0.080), 1.92 mmHg at 60 ± 15 days (P = 0.110), and 6.18 mmHg (P = 0.001) at 180 ± 30 days. CONCLUSION: Topical difluprednate is a well-tolerated and effective treatment for noninfectious uveitic cystoid macular edema with decreased central foveal thickness, mild improvement in visual acuity, and elevation of intraocular pressure observed in a few patients.

Sustained-release dexamethasone intravitreal implant in juvenile idiopathic arthritis-related uveitis.

The purpose of this study is to review the results of treatment of juvenile idiopathic arthritis-related uveitis with the use of intravitreal dexamethasone implant. Sixteen eyes with Juvenile idiopathic arthritis (JIA)-associated uveitis received intravitreal dexamethasone implant to treat recalcitrant anterior segment inflammation (43.7 %), chronic macular edema (6.2 %), or a combination of both (50 %). One month after injection, mean visual acuity had improvement to 39.6 ± 11 ETDRS letters (p < 0.001). Mean AC cells measure at 1 month was 0.79 and 0.75 at 3 months. One month after injection, there was a significant reduction of central retinal thickness (CRT) to 342.4 ± 79.3 µm (p < 0.01). One month after the second implant, 11 eyes (91.6 %) achieved improved activity of the anterior uveitis, and mean best-corrected visual acuity improved to 44.6 ± 8.1 ETDRS letters (p < 0.01). At 1 month after the second injection, 4/5 eyes had resolution of macular edema with CRT of 250.4 ± 13.7 µm (p < 0.01). Of the 16 eyes, 12 eyes received a second injection at mean of 7.5 ± 3.1 months after the first treatment, and 5 eyes received a third Ozurdex injection on average 7 ± 4.6 months after the second injection. Of the 16 eyes, five eyes were pseudophakic prior to injection. Of the remaining 11 eyes, 8 (73 %) developed worsening posterior subcapsular cataract at a mean of 7.3 ± 1.2 months after the first injection. After the first injection, only one eye required topical antiglaucoma therapy with maximum pressure of 25 mmHg. In patients with recalcitrant JIA-associated active uveitis, injection of sustained-release dexamethasone can achieve control of anterior inflammation and resolution of macular edema.

Anterior segment spectral domain optical coherence tomography imaging of patients with anterior scleritis.

The purpose of the study was to describe the findings seen on anterior segment spectral domain optical coherence tomography (SD-OCT) in patients with anterior scleritis and determine the feasibility of using SD-OCT to image and grade the degree of scleral inflammation and monitor response to treatment. All patients underwent slit lamp examination by a uveitis specialist, and the degree of scleral inflammation was recorded. Spectral domain OCT imaging was then performed of the conjunctiva and scleral tissue using a standardized acquisition protocol. The scans were graded and compared to clinical findings. Twenty-eight patients with anterior scleritis and ten patients without ocular disease were included in the study. Seventeen of the scleritis patients were followed longitudinally. Common findings on SD-OCT in patients with active scleritis included changes in hyporeflectivity within the sclera, nodules, and visible vessels within the sclera. There was significant variation in findings on SD-OCT within each clinical grade of active scleritis. These changes on SD-OCT improved with treatment and clinical improvement. SD-OCT imaging provided various objective measures that could be used in the future to grade inflammatory activity in patients with anterior scleritis. Longitudinal imaging of patients with active scleritis demonstrated that SD-OCT may have great utility in monitoring response to treatment.

Genetic of uveitis.

Immune-mediated uveitis may be associated with a systemic disease or may be localized to the eye. T-cell-dependent immunological events are increasingly being regarded as extremely important in the pathogenesis of uveitis. Several studies have also shown that macrophages are major effectors of tissue damage in uveitis. Uveitis phenotypes can differ substantially, and most uveitis diseases are considered polygenic with complex inheritance patterns. This review attempts to present the current state of knowledge from in vitro and in vivo research on the role of genetics in the development and clinical course of uveitis. A review of the literature in the PubMed, MEDLINE, and Cochrane databases was conducted to identify clinical trials, comparative studies, case series, and case reports describing host genetic factors as well as immune imbalance which contribute to the development of uveitis. The search was limited to primary reports published in English with human subjects from 1990 to the present, yielding 3590 manuscripts. In addition, referenced articles from the initial searches were hand searched to identify additional relevant reports. After title and abstract selection, duplicate elimination, and manual search, 55 papers were selected for analysis and reviewed by the authors for inclusion in this review. Studies have demonstrated associations between various genetic factors and the development and clinical course of intraocular inflammatory conditions. Genes involved included genes expressing interleukins, chemokines, chemokine receptors, and tumor necrosis factor and genes involved in complement system. When considering the genetics of uveitis, common threads can be identified. Genome-wide scans and other genetic methods are becoming increasingly successful in identifying genetic loci and candidate genes in many inflammatory disorders that have a uveitic component. It will be important to test these findings as uveitis-specific genetic factors. Therefore, the burgeoning understanding of the human genome promises to result in new insight into the pathogenesis of uveitis.