Visual Outcomes and Risk of Endophthalmitis in Open Globe Injuries without Intraocular Foreign Bodies with Delayed Repair.

OBJECTIVE: To assess and compare the rate of endophthalmitis and visual outcomes in cases of OGI's without intraocular foreign bodies repaired within and greater than 24 hours from the time of injury. DESIGN: A retrospective review of 2,002 cases of OGI's presenting to a single institution. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Patients with OGI's were admitted and managed according to a standardized protocol. METHODS, INTERVENTION, OR TESTING: The impact of timing of repair was assessed between those undergoing OGI repair within (i) 24 hours, (ii) 25-36 hours, and (iii) greater than 36 hours from the time of injury. MAIN OUTCOME AND MEASURE: Rates of endophthalmitis and postoperative visual acuity of logMAR 1.3, logMAR 1.0, and logMAR 0.3 at 180 days and 1 year following open globe repair. RESULTS: 1,382 patients with OGI's were included, of which 75% were male with an average age of 41 years. Maximal zone of injury was zone 1 for 468 patients, zone 2 for 529 patients and zone 3 for 508 patients. 84% of all OGI's underwent repair within 24 hours from the time of injury, 9% from 25-36 hours, and 7% greater than 36 hours. Average preoperative visual acuity was hand motion. Risk factors associated with repair performed greater than 36 hours from the time of injury included female sex (p=0.042). Endophthalmitis was associated with time to repair greater than 36 hours (p=0.049) but not with 25-36 hours or zone of injury (p=0.111). Time to repair had no significant impact on visual acuity outcomes. CONCLUSIONS: Although repair of OGI's within 24 hours is the current standard of care, this study found no statistically significant difference in rates of endophthalmitis or visual outcomes in eyes undergoing repair within 24 hours of injury compared to repair extending to 25 to 36 hours . Endophthalmitis rates did increase after 36 hours. We recommend urgent repair of open globe injuries, but in certain circumstances, it may be reasonable to delay repair beyond 24 hours to optimize operating conditions.

Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography.

PURPOSE: To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6 mm and Montage 15 × 15 mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. RESULTS: Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). CONCLUSION: WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.

EPIRETINAL MEMBRANE WITH FOVEAL HERNIATION: Visual and Surgical Outcomes.

PURPOSE: Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. METHODS: A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. RESULTS: A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P < 0.0001). The average central retinal thickness decreased from 632 µm to 432 µm (P < 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P < 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P < 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P < 0.05) on spectral domain optical coherence tomography. CONCLUSION: Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients' BCVA and microstructural abnormalities.

Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial.

PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM. DESIGN: Prospective, open-label, nonrandomized, dose-escalation, phase I/II clinical trial. PARTICIPANTS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS: Patients received uniocular subfoveal injections of low-dose (up to 5 × 1010 vector genome [vg] per eye, n = 5) or high-dose (up to 1 × 1011 vg per eye, n = 10) of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA (AAV2-hCHM). Patients were evaluated preoperatively and postoperatively for 2 years with ophthalmic examinations, multimodal retinal imaging, and psychophysical testing. MAIN OUTCOME MEASURES: Visual acuity, perimetry (10-2 protocol), spectral-domain OCT (SD-OCT), and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. Visual acuity returned to within 15 letters of baseline in all but 2 patients (1 developed acute foveal thinning, and 1 developed a macular hole); the rest showed no gross changes in foveal structure at 2 years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry or in the lateral extent of retinal pigment epithelium relative preservation by SD-OCT and SW-FAF. Microperimetry showed nonsignificant (< 3 standard deviations of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: Visual acuity was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13 of 15 patients. Acute foveal thinning with unchanged perifoveal function in 1 patient and macular hole in 1 patient suggest foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.

Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study.

PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.

RETINAL DETACHMENT WITH INFERIOR RETINAL BREAKS: Primary Vitrectomy Versus Vitrectomy With Scleral Buckle (PRO Study Report No. 9).

INTRODUCTION: Rhegmatogenous retinal detachments with inferior retinal breaks are believed to have a higher risk of recurrent rhegmatogenous retinal detachment. This study compared anatomic and visual outcomes between primary pars plana vitrectomy (PPV) and combination PPV with scleral buckle (PPV/SB) for rhegmatogenous retinal detachments with inferior retinal breaks. METHODS: This is an analysis of the Primary Retinal Detachment Outcomes study, a multi-institutional cohort study of consecutive primary rhegmatogenous retinal detachment surgeries from January 1, 2015, through December 31, 2015. The primary outcome was single-surgery success rate. Only eyes with inferior retinal breaks (one break in the detached retina between five and seven o'clock) were included. RESULTS: There were 238 eyes that met the inclusion criteria, 95 (40%) of which underwent primary PPV and 163 (60%) that underwent combined PPV/SB. The single-surgery success rate was 76.8% for PPV and 87.4% for PPV/SB (P = 0.0355). This remained significant on multivariate analysis (P = 0.01). Subgroup analysis showed that a superior single-surgery success rate of PPV/SB was especially noted in phakic eyes (85.2% vs. 68.6%; P = 0.0464). CONCLUSION: Retinal detachment with inferior retinal breaks had a higher single-surgery success rate if treated with PPV/SB compared with PPV alone, particularly in phakic eyes.

CHARACTERISTICS AND SURGICAL OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT IN OLDER ADULTS: A Multicenter Comparative Cohort Study.

PURPOSE: To describe characteristics and outcomes of primary rhegmatogenous retinal detachment in older adults (age ≥ 80). METHODS: Consecutive patients with rhegmatogenous retinal detachment undergoing pars plana vitrectomy (PPV), scleral buckling (SB), or PPV/SB in the Primary Retinal Detachment Outcomes Study were evaluated. Outcome measures included single surgery anatomic success and visual acuity. RESULTS: Of 2,144 patients included, 125 (6%) were 80 years or older. Compared with younger patients (age 40-79), older adults were more likely to be pseudophakic (P < 0.001), have macula-off detachments (P < 0.001), and have preoperative proliferative vitreoretinopathy (P = 0.02). In older adults, initial surgery was PPV in 73%, PPV/SB in 27%, and primary SB in 0%. Single surgery anatomic success was 78% in older adults compared with 84% in younger patients (P = 0.03). In older adults, single surgery anatomic success was 74% for PPV and 91% for PPV/SB (P = 0.03). The final mean logMAR was lower for older adults (0.79 [20/125] vs. 0.40 [20/40], [P < 0.001]). In older adults, the final mean logMAR for eyes that underwent PPV was 0.88 (20/160) compared with 0.50 (20/63) for PPV/SB (P = 0.03). CONCLUSION: Octogenarians and nonagenarians presented with relatively complex pseudophakic rhegmatogenous retinal detachments. Single surgery anatomic success and visual outcomes were worse compared with younger patients, and PPV/SB had better outcomes compared with PPV alone.

Primary Retinal Detachment Outcomes Study: Pseudophakic Retinal Detachment Outcomes: Primary Retinal Detachment Outcomes Study Report Number 3.

PURPOSE: This study evaluates outcomes of comparable pseudophakic rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy (PPV) or PPV with scleral buckle (PPV-SB). DESIGN: Multicenter, retrospective, interventional cohort study. PARTICIPANTS: Data were gathered from patients from multiple retina practices in the United States with RRD in 2015. METHODS: A large detailed database was generated. Pseudophakic patients with RRD managed with PPV or PPV-SB were analyzed for anatomic and visual outcomes. Eyes with proliferative vitreoretinopathy, giant retinal tears, previous invasive glaucoma surgery, and ≤90 days of follow-up were excluded from outcomes analysis. Single surgery anatomic success (SSAS) was defined as retinal attachment without ongoing tamponade and with no other RRD surgery within 90 days. MAIN OUTCOME MEASURES: Single surgery anatomic success and final Snellen visual acuity (VA). RESULTS: A total of 1158 of 2620 eyes (44%) with primary RRD were pseudophakic. A total of 1018 eyes had greater than 90 days of follow-up. Eyes with proliferative vitreoretinopathy, previous glaucoma surgery, and giant retinal tears were excluded, leaving 893 pseudophakic eyes eligible for outcome analysis. A total of 461 (52%) were right eyes. A total of 606 patients (67%) were male, with a mean age of 65±11 years. Pars plana vitrectomy and PPV-SB as the first procedure were performed on 684 eyes (77%) and 209 eyes (23%), respectively. The mean follow-up was 388±161 days, and overall SSAS was achieved in 770 eyes (86%). Single surgery anatomic success was 84% (577/684) for PPV and 92% (193/209) for PPV-SB. The difference in SSAS between types of treatment was significant (P = 0.009). In eyes with macula-on RRD, SSAS was 88% in eyes treated with PPV and 100% in eyes treated with PPV-SB (P = 0.0088). In eyes with macula-off RRD, SSAS was 81% in eyes treated with PPV and 89% in eyes treated with PPV-SB (P = 0.029). Single surgery anatomic success was greater for PPV-SB than PPV for inferior (96% vs. 82%) and superior (90% vs. 82%) detachments. Mean final VA was similar for PPV (20/47) and PPV-SB (20/46; P = 0.805). CONCLUSIONS: In pseudophakic RRDs, SSAS was better in patients treated with PPV-SB compared with PPV alone, whereas visual outcomes were similar for both groups.

Primary Retinal Detachment Outcomes Study Report Number 2: Phakic Retinal Detachment Outcomes.

PURPOSE: Anatomically similar rhegmatogenous retinal detachments (RRDs) can be treated with scleral buckle (SB), pars plana vitrectomy (PPV), or SB combined with PPV (PPV/SB). This study compares moderately complex phakic primary RRD treated with SB, PPV, or PPV/SB to review anatomic and visual outcomes. DESIGN: Multicenter, retrospective, interventional cohort study. PARTICIPANTS: Data were gathered on all patients from multiple retina practices in the United States with RRD in 2015 and >90 days of follow-up. The cohort of phakic patients with moderately complex RRD was analyzed. METHODS: A large and detailed database was generated. Eyes with findings that would bias toward PPV (vitreous hemorrhage, dense cataract, proliferative vitreoretinopathy, giant retinal tear, among others) were excluded. Age <40 years (bias toward SB) was excluded. Comparable cases of moderately complex RRD were then chosen naive to surgeon, surgery, and outcome for subgroup analysis. MAIN OUTCOME MEASURES: Single surgery anatomic success (SSAS), defined as retinal attachment with no other RRD surgery within 90 days, is the main outcome measure. Final visual acuity is the secondary outcome measure. Pearson's chi-square and analysis of variance were used to test treatment effect of surgery type on SSAS and vision. RESULTS: Single surgery anatomic success was noted in 155 of 169 SB cases (91.7%), 207 of 249 PPV cases (83.1%), and 271 of 297 PPV/SB cases (91.2%). Scleral buckle and PPV/SB were superior to PPV for SSAS (P = 0.0041). For macula-on or split cases, SB had significantly better visual outcomes than PPV or PPV/SB even after controlling for cataract (cases with minimal cataract at final follow-up or after cataract surgery) (P < 0.001). CONCLUSIONS: For phakic moderately complex primary RRDs in this study of PPV versus SB versus PPV/SB, SB had the best visual outcomes, and PPV had the worst SSAS outcomes.

POSTERIORLY INSERTED VITREOUS BASE: Preoperative Characteristics, Intraoperative Findings, and Outcomes After Vitrectomy.

PURPOSE: To determine the preoperative characteristics, intraoperative and postoperative complications, and outcomes of eyes with posteriorly inserted vitreous base. METHODS: In this retrospective, observational, consecutive case series at 2 academic centers, 37 patients were studied who had posteriorly inserted vitreous base noted during vitrectomy. Posteriorly inserted vitreous base was defined as the insertion of the posterior hyaloid membrane being located posterior to the vortex veins. Fifteen eyes were analyzed in a histopathologic study of donor eyes to determine the average distance of the ora serrata from the vortex veins as this distance is uncertain. RESULTS: Posteriorly inserted vitreous base was identified during vitrectomy in 31 eyes with rhegmatogenous retinal detachment (84%), 4 with macular hole (11%), 1 with vitreous hemorrhage, and 1 with epiretinal membrane. Adjunctive buckle was used in 24%; 54% had 360° laser. Average number of tears seen preoperatively in those with rhegmatogenous retinal detachment was 3.1. Thirty percent had new breaks identified intraoperatively. Forty-one percent had lattice degeneration; new breaks were found in 40% of eyes with lattice. Thirteen percent of rhegmatogenous retinal detachments developed proliferative vitreoretinopathy. Average distance from the ora serrata to the vortex veins was 7.6 mm. CONCLUSION: Any eye undergoing vitrectomy may have posteriorly inserted vitreous base, but those with a high number of retinal breaks and lattice near the equator may be at highest risk. Redetachment and proliferative vitreoretinopathy still occur despite knowledge of the disorder and adjuvant treatments.

FACTORS ASSOCIATED WITH THE USE OF 360-DEGREE LASER RETINOPEXY DURING PRIMARY VITRECTOMY WITH OR WITHOUT SCLERAL BUCKLE FOR RHEGMATOGENOUS RETINAL DETACHMENT AND IMPACT ON SURGICAL OUTCOMES (PRO STUDY REPORT NUMBER 4).

PURPOSE: To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS: This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. RESULTS: Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). CONCLUSION: Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial.

PURPOSE: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy. DESIGN: Randomized sham-controlled clinical trial. PARTICIPANTS: Ninety-nine study eyes of 67 eligible participants were enrolled. METHODS: Single-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure. MAIN OUTCOME MEASURES: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups. RESULTS: Among the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group. CONCLUSIONS: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.

APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective Trial. Report No. 2.

PURPOSE: We sought to characterize the angiofibrotic and apoptotic effects of vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal membranes in eyes with traction retinal detachment because of proliferative diabetic retinopathy. METHODS: Membranes were excised from 20 eyes of 19 patients (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes were stained with antibodies targeting connective tissue growth factor (CTGF) or VEGF and colabeled with antibodies directed against endothelial cells (CD31), myofibroblasts, or retinal pigment epithelium markers. Quantitative and colocalization analyses of antibody labeling were obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining were performed. RESULTS: High levels of fibrosis were observed in both groups. Cell apoptosis was higher (P = 0.05) in bevacizumab-treated membranes compared with controls. The bevacizumab group had a nonsignificant reduction in colocalization in CD31-CTGF and cytokeratin-VEGF studies compared with controls. Vascular endothelial growth factor in extracted membranes was positively correlated with vitreous levels of VEGF; CTGF in extracted membranes was negatively correlated with vitreous levels of CTGF. CONCLUSION: Bevacizumab suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in diabetic membranes that may be explained by high baseline levels of fibrosis. Bevacizumab may cause apoptosis within fibrovascular membranes.

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.

Validation of the Retinal Detachment after Open Globe Injury (RD-OGI) Score as an Effective Tool for Predicting Retinal Detachment.

PURPOSE: The Retinal Detachment after Open Globe Injury (RD-OGI) Score is a clinical prediction model that was developed at the Massachusetts Eye and Ear Infirmary to predict the risk of retinal detachment (RD) after open globe injury (OGI). This study sought to validate the RD-OGI Score in an independent cohort of patients. DESIGN: Retrospective cohort study. PARTICIPANTS: The predictive value of the RD-OGI Score was evaluated by comparing the original RD-OGI Scores of 893 eyes with OGI that presented between 1999 and 2011 (the derivation cohort) with 184 eyes with OGI that presented from January 1, 2012, to January 31, 2014 (the validation cohort). METHODS: Three risk classes (low, moderate, and high) were created and logistic regression was undertaken to evaluate the optimal predictive value of the RD-OGI Score. A Kaplan-Meier survival analysis evaluated survival experience between the risk classes. MAIN OUTCOME MEASURES: Time to RD. RESULTS: At 1 year after OGI, 255 eyes (29%) in the derivation cohort and 66 eyes (36%) in the validation cohort were diagnosed with an RD. At 1 year, the low risk class (RD-OGI Scores 0-2) had a 3% detachment rate in the derivation cohort and a 0% detachment rate in the validation cohort, the moderate risk class (RD-OGI Scores 2.5-4.5) had a 29% detachment rate in the derivation cohort and a 35% detachment rate in the validation cohort, and the high risk class (RD-OGI scores 5-7.5) had a 73% detachment rate in the derivation cohort and an 86% detachment rate in the validation cohort. Regression modeling revealed the RD-OGI to be highly discriminative, especially 30 days after injury, with an area under the receiver operating characteristic curve of 0.939 in the validation cohort. Survival experience was significantly different depending upon the risk class (P < 0.0001, log-rank chi-square). CONCLUSIONS: The RD-OGI Score can reliably predict the future risk of developing an RD based on clinical variables that are present at the time of the initial evaluation after OGI.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes.

PURPOSE: To expand understanding of presentation, diagnosis, and outcomes of hemorrhagic occlusive retinal vasculitis (HORV). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-six eyes of 23 patients. METHODS: The American Society of Cataract and Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) formed a joint task force to define clinical characteristics of HORV and to study its prevalence, cause, treatment, and outcomes. An online registry was established on both societies' web sites. Surveys were e-mailed to members of both societies soliciting cases of suspected HORV. A literature search was performed to uncover additional cases. MAIN OUTCOME MEASURES: Historical data including intraoperative characteristics, images, treatment regimens, and visual and anatomic outcomes. RESULTS: Characteristic findings of HORV included unremarkable postoperative day 1 undilated examination, delayed-onset painless vision loss, mild anterior chamber and vitreous inflammation, sectoral retinal hemorrhages in areas of ischemia, and predilection for venules and peripheral involvement. Based on predetermined diagnostic criteria, 36 eyes of 23 patients were diagnosed with HORV. All eyes received intraocular vancomycin via intracameral bolus (33/36), via intravitreal injection (1/36), or through the irrigation bottle (2/36). Patients sought treatment with HORV 1 to 21 days after surgery or intravitreal injection. Visual results usually were poor: 22 of 36 eyes (61%) had 20/200 or worse visual acuity and 8 of 36 eyes (22%) had no light perception (NLP). Neovascular glaucoma developed in 20 of 36 eyes (56%). Seven eyes received additional intravitreal vancomycin after surgery; 5 of these 7 eyes had NLP visual acuity at the most recent examination. Three eyes received intravitreal corticosteroids and had final visual acuities of 20/40, 20/70, and hand movements. CONCLUSIONS: Hemorrhagic occlusive retinal vasculitis is a rare, potentially devastating condition that can develop after cataract surgery or intraocular injection. All cases in this series were associated with intraocular vancomycin. Disease course and findings suggest that HORV is caused by a delayed hypersensitivity reaction to vancomycin. Early treatment with corticosteroids likely is beneficial. Subsequently, anti-vascular endothelial growth factor injections and panretinal photocoagulation are important to prevent neovascular glaucoma, a common complication. Avoidance of additional intravitreal vancomycin is recommended if HORV is suspected.

SMOKING IS A RISK FACTOR FOR PROLIFERATIVE VITREORETINOPATHY AFTER TRAUMATIC RETINAL DETACHMENT.

PURPOSE: To determine the incidence of retinal redetachment due to proliferative vitreoretinopathy after open-globe trauma in smokers and nonsmokers. METHODS: A total of 892 patients comprising 893 open-globe injuries, in whom 255 eyes were diagnosed with a retinal detachment, and 138 underwent surgical repair were analyzed in a retrospective case-control study. Time to redetachment was examined using the Kaplan-Meier method and analysis of risk factors was analyzed using Cox proportional hazards modeling. RESULTS: Within one year after retinal detachment surgery, 47% (95% CI, 39-56%) of all 138 repaired retinas redetached because of proliferative vitreoretinopathy. Being a smoker was associated with a higher rate of detachment (adjusted hazard ratio 1.96, P = 0.01). As shown in previous studies, the presence of proliferative vitreoretinopathy at the time of surgery was also an independent risk factor for failure (adjusted hazard ratio 2.13, P = 0.005). Treatment with vitrectomy-buckle compared favorably to vitrectomy alone (adjusted hazard ratio 0.58, P = 0.04). Only 8% of eyes that redetached achieved a best-corrected visual acuity of 20/200 or better, in comparison to 44% of eyes that did not redetach (P < 0.001). CONCLUSION: Proliferative vitreoretinopathy is a common complication after the repair of retinal detachment associated with open-globe trauma, and being a smoker is a risk factor for redetachment. Further study is needed to understand the pathophysiologic mechanisms underlying this correlation.

Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies.

BACKGROUND: Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients. METHODS: In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt's macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years). Three dose cohorts (50,000, 100,000, and 150,000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations. The studies are registered with ClinicalTrials.gov, numbers NCT01345006 (Stargardt's macular dystrophy) and NCT01344993 (age-related macular degeneration). FINDINGS: There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16-25 points 3-12 months after transplantation in patients with atrophic age-related macular degeneration and 8-20 points in patients with Stargardt's macular dystrophy. INTERPRETATION: The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement. FUNDING: Advanced Cell Technology.

Clinical and Ultrastructural Studies of Epiretinal Pigmentary Deposits after Retinectomy with Silicone Oil.

PURPOSE: Large relaxing retinectomies have become increasingly used in the repair of retinal detachment related to proliferative vitreoretinopathy (PVR). Retinectomies expose the retinal pigment epithelium (RPE) to the vitreous cavity; the direct effects of silicone oil on the RPE are only beginning to be understood. DESIGN: Retrospective case series. PARTICIPANTS: Twelve patients noted to develop pigmented epiretinal deposits at regularly scheduled follow-up visits after repair of complex retinal detachments using silicone oil tamponade and retinectomy. METHODS: Epiretinal pigment deposits were characterized clinically by wide-field color photography, fundus autofluorescence imaging, and spectral-domain optical coherence tomography (SD OCT). At the time of silicone oil removal, the pigmented membranes were preserved in fixative and analyzed by light microscopy/immunostaining or electron microscopy for histologic characterization. MAIN OUTCOME MEASURES: Not applicable. RESULTS: We describe the development of diffuse preretinal pigmentary deposits in 12 eyes after surgery for complicated PVR detachments using retinectomies with oil, with an average onset of 3.2 months postoperatively. These pigment clumps produced a striking leopard-spot pattern on fundus autofluorescence imaging. Histopathologic and ultrastructural analysis of these epiretinal proliferations peeled at the time of silicone oil removal revealed RPE cells with intracellular silicone oil droplets, singly dispersed membrane-bound melanin granules, glial tissue (1 case), and a fibrous stroma. CONCLUSIONS: Although in vitro studies have suggested that RPE cells can phagocytose emulsified oil droplets, this report represents the first in vivo documentation by electron microscopy of this phenomenon in patients. These findings underscore that direct contact with silicone oil may affect the behavior of the RPE, which may be clinically relevant in patients who have undergone large relaxing retinectomies with silicone oil tamponade for PVR-related retinal detachments.

A Phase 1 Study of Intravitreous E10030 in Combination with Ranibizumab in Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the safety and tolerability of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, when administered in combination with an anti-vascular endothelial growth factor (VEGF) agent, ranibizumab (Lucentis; Genentech, South San Francisco, CA) 0.5 mg, by intravitreal injection in participants with neovascular age-related macular degeneration (NVAMD). DESIGN: Prospective phase 1 clinical trial. PARTICIPANTS: A total of 23 participants diagnosed with NVAMD and aged 50 years or older were enrolled. METHODS: Part 1 included 15 participants. Three participants received a single intravitreal E10030 (0.03 mg) injection and were subsequently given intravitreal ranibizumab (0.5 mg) injections at weeks 2, 6, and 10. Twelve participants (3 per group) received E10030 (0.03, 0.3, 1.5, or 3.0 mg) in combination with ranibizumab (0.5 mg) at day 0, month 1, and month 2 in an ascending manner. In Part 2 (8 participants), E10030 (0.3, 1.5, or 3.0 mg) in combination with ranibizumab (0.5 mg) was injected at day 0, month 1, and month 2. MAIN OUTCOME MEASURES: Safety at week 12 was the primary outcome and included assessment of vital signs, laboratory tests, and serial eye examinations. Other safety metrics included assessment through week 24 of Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and biomarker changes evaluated by optical coherence tomography (OCT) and fluorescein angiography (FA). RESULTS: All doses of intravitreal E10030 administered in combination with ranibizumab were well tolerated. No dose-limiting toxicities or relevant safety events were noted at any dose level during the study. Investigators did not report adverse events related to E10030 or ranibizumab. Mean VA change was a gain of 14 letters, and 59% of participants gained ≥15 letters from baseline at week 12. On FA at week 12, there was an 85.5% mean reduction from baseline in choroidal neovascularization (CNV) size. On OCT at the week 12 visit, there was a mean decrease in center point thickness and central subfield thickness of 38.9% and 33.7%, respectively. CONCLUSIONS: Intravitreal E10030 administered at doses up to 3 mg in combination with ranibizumab was well tolerated without evidence of systemic or ocular toxicity in participants with NVAMD. The changes in both mean VA and imaging biomarkers suggest a favorable short-term safety profile for the combination therapy of E10030 and ranibizumab.