Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.

LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.

RETINAL VASCULITIS OR VASCULAR OCCLUSION AFTER BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Systematic Review of Real-World Evidence.

PURPOSE: Retinal vasculitis or vascular occlusion (RV/RO) have been reported after brolucizumab for neovascular age-related macular degeneration. This systematic literature review evaluated RV/RO events after brolucizumab in real-world practice. METHODS: Systematic literature searches identified 89 publications; 19 were included. RESULTS: Publications described 63 patients (70 eyes) with an RV/RO event following brolucizumab. Mean age was 77.6 years and 77.8% of patients were women; 32 eyes (45.7%) received one brolucizumab injection before RV/RO. Mean (range) time to event from last brolucizumab injection was 19.4 (0-63) days, with 87.5% of events occurring within 30 days. Among eyes with preevent and postevent visual acuity (VA) assessments, 22/42 eyes (52.4%) showed unchanged (±0.08 logMAR) or improved vision from last recorded preevent assessment at latest follow-up, whereas 15/42 eyes (35.7%) showed ≥0.30 logMAR (≥15 letters) VA reduction. Patients with no VA loss were on average slightly younger and had a higher proportion of nonocclusive events. CONCLUSION: Most RV/RO events reported after brolucizumab in early real-world practice occurred in women. Among eyes with VA measurements, approximately half experienced VA loss; overall, about one-third had VA reduction of ≥0.30 logMAR at latest follow-up, with indications of regional variations.

27-GAUGE PARS PLANA/PLICATA VITRECTOMY FOR PEDIATRIC VITREORETINAL SURGERY.

PURPOSE: To report on the feasibility of 27-gauge (G) vitrectomy for pediatric patients. METHODS: This study is an international, multicenter, retrospective, interventional case series. Participants were patients 17 years or younger who underwent 27-G vitrectomy for various indications. RESULTS: The records of 56 eyes from 47 patients were reviewed. Mean age was 5.7 ± 5.2 years. Diagnoses included retinopathy of prematurity (Stages 3 with vitreous hemorrhage, 4A, 4B, and 5), Terson's syndrome, traumatic macular hole, posterior capsular opacification, endophthalmitis, and others. Instruments used were the 27-G infusion, 27-G vitreous cutter, 27-G light pipe, and 27-G internal limiting membrane forceps. Instrument bending was noted in one (1.8%) case. There were no cases with intraoperative complications, infusion issues, or postoperative endophthalmitis. There were 67/145 (46%) sclerotomies that required suturing, of which most (51/145) were sutured out of precaution. There were four cases (7.1%) that required conversion to a larger gauge and three cases (5.3%) that developed postoperative hypotony. Mean visual acuity improved from logarithm of the minimum angle of resolution 1.32 (20/420) to 0.72 (20/105), after a mean follow-up of 125.1 days (P = 0.01). Anatomic success was achieved in 96.4% of eyes after a single surgery. CONCLUSION: Twenty-seven-gauge vitrectomy was safe and feasible in selected pediatric vitreoretinopathies. Further studies are warranted to examine indications and outcomes.

LONG-TERM VISUAL OUTCOMES AND THE TIMING OF SURGICAL REPAIR OF FOVEA-SPLITTING RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments. METHOD: A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair. RESULTS: One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P = <0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P = <0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481). CONCLUSION: We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.

FEATURES AND OUTCOMES OF EYES THAT UNDERWENT SURGICAL REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENTS AFTER BEING TREATED FOR ACUTE ENDOPHTHALMITIS.

PURPOSE: To evaluate the etiology, clinical course, and outcomes of eyes that suffered postendophthalmitis rhegmatogenous retinal detachments. METHODS: A retrospective, consecutive case series was conducted of patients managed at Associated Retinal Consultants P.C. from January 2013 to December 2019. Patients were identified as having had endophthalmitis by ICD-9/10 codes. Those with endophthalmitis and/or rhegmatogenous retinal detachment not managed at Associated Retinal Consultants from January were excluded. RESULTS: Charts of 413 patients were reviewed and 19 met inclusion criteria. Incidence of rhegmatogenous retinal detachment following infectious endophthalmitis was 4.6%. The most common inciting events for endophthalmitis was intravitreal injection (9 of 19) and cataract surgery (7 of 19). Fifteen of 19 patients were treated with an injection of intravitreal antibiotics and 4 underwent immediate vitrectomy with antibiotic injection. Biopsy cultures were obtained in 18 of 19 patients and yielded positive growth in 12 (66.7%). Seventeen of the 19 eyes were operable. Final retinal reattachment rate was 88.2% (15 of 17). Mean final logMAR visual acuity was 1.58 (Snellen 20/765). Factors associated with worse final visual acuity after surgical repair included preceding intravitreal injection (P = 0.001), streptococcus species (P = 0.024), presence of proliferative vitreoretinopathy (P = 0.015), and use of silicone oil during primary rhegmatogenous retinal detachment repair (P = 0.010). CONCLUSION: Rhegmatogenous retinal detachments following endophthalmitis occur infrequently. Although most eyes can be repaired surgically, visual outcomes are often poor, particularly in eyes that were infected with streptococcal species and had associated proliferative vitreoretinopathy.

REFRACTIVE OUTCOMES AFTER SUTURELESS INTRASCLERAL FIXATION OF INTRAOCULAR LENS WITH PARS PLANA VITRECTOMY.

PURPOSE: To evaluate the refractive outcomes of sutureless intrascleral fixation of intraocular lens with pars plana vitrectomy. METHOD: A retrospective, consecutive cohort from multiple surgeons of a single center. Primary outcomes included spherical equivalent (SEQ) and change in SEQ (ΔSEQ) from preoperative intraocular lens power calculations. Secondary outcomes included refractive outcomes of fixation at 1.5 mm, 2 mm, and 2.5 mm posterior to the limbus. RESULTS: In total, 84 eyes of 80 patients were included. Preoperative logarithm of the minimum angle of resolution visual acuity was 1.21 ± 0.68 (20/320). The mean follow-up time was 2.33 ± 1.36 years. At 3 months, SEQ was -0.50 ± 1.59 D and ΔSEQ was 0.58 ± 1.49 D. At 1 year, SEQ was -0.55 ± 1.32 D and ΔSEQ was 0.39 ± 1.42 D. At the last follow-up, logarithm of the minimum angle of resolution visual acuity was 0.34 ± 0.34 (20/40), SEQ was -0.51 ± 1.44 D, and ΔSEQ was 0.57 ± 1.27 D. There was no difference between SEQ or ΔSEQ throughout follow-up (P = 0.97 and P = 0.96, respectively). At fixation distances more posterior to the limbus, mean ΔSEQ was more hyperopic at 3 months, 1-year, and the last follow-up (P = 0.02, P = 0.01, and P = 0.006, respectively). CONCLUSION: Refractive outcomes for sutureless intrascleral fixation of intraocular lens with pars plana vitrectomy were favorable and showed stability postoperatively. These results may aid surgeons achieve better desired refractive outcomes for this technique.

Autologous Retinal Transplantation for Primary and Refractory Macular Holes and Macular Hole Retinal Detachments: The Global Consortium.

PURPOSE: To report the anatomic and functional outcomes of autologous retinal transplantation (ART). DESIGN: Multicenter, retrospective, interventional, consecutive case series. PARTICIPANTS: One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. METHODS: All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. MAIN OUTCOME MEASURES: Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. RESULTS: One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P < 0.001) after surgery (mean follow-up, 8.6 ± 0.8 months). Autologous retinal transplantation was performed for primary MH repair in 27% of patients (n = 35), for refractory MH in 58% of patients (n = 76; mean number of previous surgeries, 1.6 ± 0.2), and for MH-RRD in 15% of patients (n = 19). Mean maximum MH diameter was 1470 ± 160 µm, mean minimum diameter was 840 ± 94 µm, and mean axial length was 24.6 ± 3.2 mm. Overall, 89% of MHs closed (78.5% complete; 10% small eccentric defect), with a 95% closure rate in MH-RRD (68.4% complete; 26.3% small eccentric defect). Visual acuity improved by at least 3 lines in 43% of eyes and by at least 5 lines in 29% of eyes. Reconstitution of the EZ (P = 0.02) and ANL (P = 0.01) on OCT were associated with better final VA. Five cases of ART graft dislocation (3.8%), 5 cases of postoperative retinal detachment (3.8%), and 1 case of endophthalmitis (0.77%) occurred. CONCLUSIONS: In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

PERIPHERAL RETINAL ANGIOGRAPHIC FINDINGS IN MACULAR TELANGIECTASIS TYPE 2.

PURPOSE: To evaluate the retinal periphery in patients with idiopathic juxtafoveal telangiectasis or macular telangiectasis Type 2 (MacTel2), using widefield fluorescein angiography. METHODS: Single-center, retrospective, observational case series of 50 eyes of 50 patients with MacTel2 and 50 eyes of 50 age-matched controls. RESULTS: Thirty-seven eyes in the MacTel2 group (74%) showed peripheral capillary nonperfusion or dropout, compared with 37 eyes in the control group (74%, P = 1.0). Morphologically, the MacTel2 group trended toward having a higher proportion of pruning-type capillary dropout (44%) compared with controls (28%), but this was not statistically significant (P = 0.12). Patients with MacTel2 had a higher incidence of microaneurysms compared with controls (MacTel2 56%; controls 42%; P = 0.048), independent of age or systemic risk factors. There was no difference in the incidence of venous-venous shunts (MacTel2 10%; controls 10%; P = 1.0), arteriovenous shunts (MacTel2 14%; controls 18%; P = 0.60), venous tortuosity (MacTel2 60%; controls 66%; P = 0.58), or arterial tortuosity (MacTel2 54%; controls 68%; P = 0.20), which was mild in most cases. CONCLUSION: We note a high incidence of peripheral vascular and retinal findings in both patients with MacTel2 and age-matched controls, using widefield fluorescein angiography. Patients with MacTel2 had significantly more microaneurysms, independent of age or other systemic risk factors.

Clinical Course and Characteristics of Eyes with Recurrent Episodes of Endophthalmitis.

PURPOSE: Infectious endophthalmitis is a devastating, yet rare, complication after intraocular surgery, trauma, and systemic illness. Given its rare incidence, few patients would be expected to experience more than 1 episode of infectious endophthalmitis in their lifetime. We reviewed our patients who were diagnosed with and treated for at least 2 separate episodes of endophthalmitis. DESIGN: A retrospective, consecutive case series was conducted of patients managed at Associated Retinal Consultants PC (Royal Oak, Michigan) from January 2013 through December 2019. PARTICIPANTS: Patients were identified with the diagnosis of endophthalmitis by International Classification of Diseases, Ninth and Tenth Editions, codes. METHODS: Those diagnosed and then treated either with a vitreous tap and intravitreal injection of antibiotics or with pars plana vitrectomy at least twice were included. Those treated multiple times for the same episode of endophthalmitis were excluded. MAIN OUTCOME MEASURES: Cause and risk factors for recurrent endophthalmitis. RESULTS: Charts of 535 patients were reviewed, and 12 patients met inclusion criteria. The median age at initial presentation was 72.5 years, and 33.3% were men. Eight of the 12 patients (66%) experienced recurrent endophthalmitis in the same eye, and 4 of the 12 patients (33%) experienced separate episodes in different eyes. The average time between episodes was 604 days (range, 90-2366 days). The average follow-up from the second episode was 492 days (range, 119-1185 days). The most common cause for both the first and second episodes was recent intravitreal injection (50% and 58.3%, respectively) followed by surgery associated (41.6% and 33.3%, respectively). The cause was the same for the first and second episodes of 8 patients (75%). Of the 24 recorded episodes of endophthalmitis, culture results were positive in 41.6%, with coagulase-negative Staphylococcus being the most common bacteria identified. CONCLUSIONS: Recurrent endophthalmitis is rare and seen most commonly after intravitreal injections. Most patients in this series showed culture-negative results. Each successive episode of endophthalmitis was associated with a worse final visual outcome. The cumulative number of intravitreal injections may be an independent risk factor for recurrent postinjection endophthalmitis.

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes.

PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multicenter, interventional, retrospective case-control study. PARTICIPANTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery. MAIN OUTCOME MEASURES: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026). CONCLUSIONS: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.

Predictors of Endophthalmitis after Intravitreal Injection: A Multivariable Analysis Based on Injection Protocol and Povidone Iodine Strength.

PURPOSE: To determine the incidence of endophthalmitis after anti-vascular endothelial growth factor (VEGF) therapy at our institution and to identify potential risk factors for endophthalmitis occurring after injection. DESIGN: Retrospective, single-center cohort study. PARTICIPANTS: All patients who received an intravitreal injection of an anti-VEGF medication between January 1, 2014, and March 31, 2017. METHODS: Current Procedural Terminology and International Classification of Diseases billing codes were used to identify instances of anti-VEGF administration and cases of endophthalmitis. Medical records and injection technique were reviewed carefully in each case. Multivariable logistic regression analysis was performed in a stepwise fashion to determine independent predictors of endophthalmitis based on injection protocol. MAIN OUTCOME MEASURES: Incidence of endophthalmitis after injection and odds of endophthalmitis by injection technique with 95% confidence intervals (CIs). RESULTS: A total of 154 198 anti-VEGF injections were performed during the period of interest, resulting in 58 cases of endophthalmitis (0.038% [1:2659]). After adjustment for confounders, both 2% lidocaine jelly (odds ratio [OR], 11.28; 95% CI, 3.39-37.46; P < 0.001) and 0.5% Tetravisc (Ocusoft, Richmond, TX; OR, 3.95; 95% CI, 1.15-13.50; P = 0.03) use were independent risk factors for endophthalmitis after injection. Lid speculum use, povidone iodine strength (5% vs. 10%), injection location (superior or inferior), conjunctival displacement, use of provider gloves, use of a strict no-talking policy, use of subconjunctival lidocaine, and topical antibiotic use were not statistically significant predictors of endophthalmitis after injection. There was no difference in endophthalmitis rate among the anti-VEGF agents (bevacizumab, ranibizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept). CONCLUSIONS: The incidence of endophthalmitis after anti-VEGF injections is low. Use of lidocaine jelly or Tetravisc may increase the risk of endophthalmitis after injection.

Scleral Transillumination With Digital Heads-Up Display: A Novel Technique for Visualization During Vitrectomy Surgery.

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

Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Choroidal Neovascularization in Fellow Eyes of Previously Treated Patients With Neovascular Age-Related Macular Degeneration.

Importance: Neovascular age-related macular degeneration (nvAMD) is a leading cause of vision loss. The optimal screening protocol to detect choroidal neovascularization (CNV) in fellow eyes of patients undergoing treatment for unilateral CNV has not been determined. Objective: To compare the visual outcomes of eyes with established, active nvAMD in index eyes with outcomes of fellow eyes that subsequently developed CNV during the management protocol. Design, Setting, and Participants: In this retrospective single-center case series conducted at a private vitreoretinal practice, data were collected for all patients treated for bilateral nvAMD between October 1, 2015, and October 1, 2016, for whom we could determine the date of index eye and fellow eye conversion to nvAMD (n = 1600). Per institutional protocol, patients were screened for new CNV in the fellow eye at every office visit. Patients were excluded if they had a condition that could result in marked asymmetric vision loss. Exposures: Development of nvAMD. Main Outcomes and Measures: Visual acuity (VA) at the time of diagnosis of nvAMD and at equivalent time points following conversion to nvAMD for both index eyes and fellow eyes. Results: A total of 264 patients met the inclusion criteria; 197 (74.6%) were women and 253 (95.8%) were white, and the mean (SD) age was 79.1 (8.2) years at time of index eye conversion to nvAMD and 80.6 (8.2) years at time of fellow eye conversion to nvAMD. Fellow eyes presented with better VA (mean VA, 20/50 [0.40 logMAR]) compared with index eyes (mean VA, 20/90 [0.67 logMAR]) at the time of conversion (difference, 14 letters [0.27 logMAR]; 95% CI, 10-17 [0.20-0.34]; P < .001). Index eyes did not achieve the same level of VA as fellow eyes after an equivalent postconversion follow-up of approximately 20 months (mean VA: index eye; 20/70 [0.56 logMAR]; fellow eye, 20/50 [0.40 logMAR]; difference, 8 letters [0.15 logMAR]; 95% CI, 4-11 [0.08-0.22]; P < .001). No difference was detected between the mean number of anti-vascular endothelial growth factor injections received by fellow eyes and index eyes (9.7 vs 10.0 injections, respectively). Conclusions and Relevance: This retrospective study suggests that fellow eyes of previously treated patients with nvAMD may achieve better VA than their index eye counterparts after an equivalent amount of follow-up. This may be because the CNV was detected and treated earlier and at a better level of VA, although it is unknown whether the frequent office visits, VA measurements, or optical coherence tomography testing was responsible for the detection at a better level of VA.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: A Clinical-Pathophysiological Analysis.

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

DEXAMETHASONE INTRAVITREAL IMPLANT FOR THE TREATMENT OF RECALCITRANT MACULAR EDEMA AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To investigate the efficacy of the intravitreal dexamethasone implant as the treatment for recalcitrant macular edema after successful rhegmatogenous retinal detachment repair. METHODS: A retrospective review of the medical records was performed on 17 consecutive patients (17 eyes) with recalcitrant macular edema associated with rhegmatogenous retinal detachment repair who were treated with a single or multiple injections of an intravitreal dexamethasone 0.7-mg implant (Ozurdex; Allergan Inc) at two centers. Main outcomes of the study were change in logarithm of the minimum angle of resolution visual acuity, measurement of central foveal thickness, and macular cube volume as measured by spectral domain optical coherence tomography and frequency of complications. RESULTS: The mean age was 67 years (range, 51-78 years). All 17 patients received previous topical therapy and 12 of them had previous administration of intravitreal triamcinolone with persistence of macular edema. Baseline mean best-corrected visual acuity was 20/100 (logarithm of the minimum angle of resolution 0.75; range, 0.18-1.3 ±0.37) in the affected eyes. There was a statistically significant improvement in best-corrected visual acuity at 1 month (P < 0.001) and 3 months (P = 0.01). Mean baseline central foveal thickness was 505 µm, and mean macular cube volume was 10.62 mm. There was a statistically significant decrease in central foveal thickness and macular cube volume at 1 month (505-290 µm, P = 0.013 and 10.62-9.13 mm, P < 0.0001) and 3 months (P = 0.01). All patients developed recurrence of macular edema at 3 months, which required retreatment. The average number of implants was 4 (range, 1-14). No adverse effects such as retinal detachment or endophthalmitis occurred. Two patients experienced an increase in intraocular pressure that was controlled with topical therapy. CONCLUSION: Macular edema that occurs in eyes after successful repair of rhegmatogenous retinal detachment can be chronic and recalcitrant, and may be successfully and safely treated with the dexamethasone intravitreal implant.

STRUCTURAL ANALYSIS AND COMPREHENSIVE SURGICAL OUTCOMES OF THE SUTURELESS INTRASCLERAL FIXATION OF SECONDARY INTRAOCULAR LENSES IN HUMAN EYES.

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

Simultaneous dexamethasone intravitreal implant and anti-VEGF therapy for neovascular age-related macular degeneration resistant to anti-VEGF monotherapy.

PURPOSE: To evaluate the efficacy of a dexamethasone intravitreal implant in combination with intravitreal anti-VEGF agents for treatment resistant neovascular age-related macular degeneration (nvAMD). METHODS: This study was designed as a single-center, retrospective interventional case series. Consecutive patients with treatment-resistant nvAMD underwent simultaneous combined injection of anti-VEGF agent and dexamethasone intravitreal implant. Eighteen patients with mean age of 81.5 years were included. Patients received average of 26.3 anti-VEGF injections before dual therapy, with mean follow up of 8.2 months after dual therapy. RESULTS: Dual therapy produced a significant mean decrease in CFT (126.3 µm), compared to a mean increase of 29.9 µm when treated with anti-VEGF monotherapy (p=0.0017). Patients also had mean decrease in MCV of -0.85 mm3 with dual therapy compared with anti-VEGF monotherapy (p=0.0014). There was a moderate correlation between the number of prior anti-VEGF injections and the magnitude of anatomic response, suggesting that shorter disease duration may positively influence response to combined treatment. Although there was a slight trend towards improved mean visual acuity after dual therapy, these differences did not reach statistical significance. Nevertheless, with combination treatment, 33% of patients gained one or more lines of vision. Dual therapy resulted in a significantly lower number of required anti-VEGF injections (4.25 vs 5.33) and an increase of the anti-VEGF injection-free interval to 1.41 months from 1.12 months during the 6 months following dual therapy compared to the same interval before dual therapy. Dual therapy was well tolerated; two eyes developed mild IOP elevation effectively managed with topical therapy and one patient developed worsening cataract. CONCLUSIONS: Combined treatment of anti-VEGF with the dexamethasone intravitreal implant is a viable alternative for treatment-resistant nvAMD, and may reduce treatment burden. Earlier treatment with dual therapy may be beneficial to maximize anatomic and visual outcomes in these patients.