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Kimberly A Drenser,1 Dante J Pieramici,2,3 Joseph M Gunn,4 Daniel F Rosberger,5 Petra Kozma,6 Mitchell S Fineman,7,8 Luc Duchateau,9 Arshad M Khanani10 1Associated Retinal Consultants P.C., Royal Oak, MI, USA; 2California Retina Consultants, Santa Barbara, CA, USA; 3California Retina Research Foundation, Santa Barbara, CA, USA; 4Southeastern Retina Associates, Kingsport, TN, USA; 5Weill-Cornell Medical College; MaculaCare, PLLC, New York, NY, USA; 6Oxurion NV (formerly ThromboGenics NV), Leuven, Belgium; 7Mid Atlantic Retina, Philadelphia, PA, USA; 8Wills Eye Hospital, Philadelphia, PA, USA; 9Ghent University, Ghent, Belgium; 10Sierra Eye Associates, Reno, NV, USACorrespondence: Kimberly A DrenserAssociated Retinal Consultants P.C., 3555 W 13 Mile Road# LL-20, Royal Oak, MI, 48073, USATel +1 248 288 2280Fax +1 248 288 5644Email kdrenser@arcpc.netPurpose: To assess generalized (GD) and focal ellipsoid zone disruption (FD) in patients with symptomatic vitreomacular adhesion (sVMA) using spectral domain optical coherence tomography (SD-OCT) following ocriplasmin.Patients and methods: OZONE was a Phase 4, retrospective study of patients with sVMA treated with a single intravitreal injection of ocriplasmin (0.125 mg). Data from adult patients with at least 6-month follow-up after ocriplasmin were included. SD-OCT was performed at baseline (within 30 days before ocriplasmin), before Day 21 post-injection (early observation, EO), and by last observation (LO) which was maximally 6 months post-injection. The main outcome measure was the development of new and the evolution of existing FD/GD at EO and LO.Results: The study enrolled 134 eyes/patients from 22 sites in the USA. At baseline, 87 eyes (64.9%) had FD, 21 eyes (15.7%) had GD and 26 eyes (19.4%) had no FD/GD. Among the eyes without FD/GD at baseline, 13 (50%) and 8 (30.8%) developed FD or GD, respectively, by EO. By LO, FD/GD improvement or resolution was seen in > 80% of these eyes. Among the eyes with FD/GD at baseline, < 40% had improving/resolving EZ integrity at LO. The absence of FD/GD at baseline was associated with less persistent FD/GD at LO (P< 0.0005). The presence of FD with MH at baseline was associated with persistent FD at LO (P=0.027).Conclusion: The fact that a large majority of eyes had FD/GD prior to ocriplasmin was unexpected and demonstrates that EZ disruptions are common in sVMA. This suggests that loss of EZ integrity may be part of the natural history of this disorder. It is hypothesized that the status of the EZ at baseline is a contributing, ocriplasmin independent modulator of subsequent EZ changes after ocriplasmin. Prospective analyses which include a sham control group would be required to test this hypothesis.Keywords: symptomatic vitreomacular adhesion, vitreomacular traction, spectral domain optical coherence tomography, macular hole

Terms related to geographic atrophy progression and ocular comorbidities are well documented in ophthalmology clinical notes, while terms related to vision-related quality of life and functional outcomes are rarely documented., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To examine the characteristics of eyes with high-risk lattice degeneration treated with laser retinopexy and determine the indications, safety, and outcomes of the treatment. Methods: This interventional single-surgeon consecutive retrospective study was conducted at Wills Eye Hospital between 2014 and 2021. The series included eyes with lattice degeneration with high-risk lesions. Documented characteristics and outcomes of these eyes and fellow eyes were documented. Results: The study comprised 167 eyes of 143 patients (53.3% women; mean age [±SD], 50 ± 17 years). Complications after laser treatment included new posterior vitreous detachment (PVD) (n = 21), epiretinal membrane (ERM) (n = 13), retinal detachment (RD) (n = 5), and additional laser required (n = 22). Eyes that developed ERMs were more likely to develop PVDs (odds ratio, 5.39; 95% CI, 1.57-18.47). Patents who developed ERMs were older (mean, 60 ± 7 years vs 49 ± 17 years; P  = .016), as were those developing PVDs (mean, 59 ± 8 years vs 48 ± 17; P  = .005). No eye with a new ERM required surgery (n = 13). Four eyes with a new RD required laser retinopexy alone; 1 eye was treated surgically. No eye had an RD at the most recent evaluation. Conclusions: Despite high-risk lesions in areas of lattice degeneration, few eyes developed RDs after prophylactic laser retinopexy. Older patients may have a higher risk for ERM or PVD after laser treatment. Eyes with post-laser PVD were more likely to develop an ERM., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Yonekawa is a consultant to Alcon, Bausch-Health, Pykus, Regeneron, Tarsus, and Versant Health. None of the other authors declared potential conflicts of interest with respect to the research, authorship, and/or publication of the article., (© The Author(s) 2024.)

Cultural differences in the experience of sleep warrant consideration in the measurement of sleep across populations. This requires careful attention to both language and culture when translating survey measures. While forward and back translation is the most commonly used approach, it has numerous limitations if used as an isolated method. Best practice guidelines recommend a multi-step team-based approach for translating questionnaires. We present our recent experience applying best practices in a study with both Spanish and English-speaking Mexican American mothers of toddlers. This work is part of a larger project that will measure parental sleep-related beliefs and parenting practices in Mexican American parents of toddlers. We utilized a team-based approach to translation and cultural adaptation, assembling a diverse, bilingual, and bicultural team. The translation process started with items and measures that we had selected, revised as needed, or created. New items were based on constructs identified in semi-structured interviews and focus groups used to explore parental sleep-related beliefs and parenting practices in the target population. Following this, our translation process included forward and back translation, harmonization and decentering, cognitive interviewing, debriefing, adjudication, and proofreading. We outline details of our process and the rationale for each step. We also highlight how each step contributes to ensuring culturally appropriate items with conceptual equivalence across languages. To ensure inclusivity and scientific rigor within the field of sleep research, investigators must utilize best practices for translations and cultural adaptations, building on the foundation of cultural constructs often identified in qualitative work., Competing Interests: Conflict of interest LJM is a consultant at Egetis Therapeutics, Harmony Biosciences, and Zepp Inc. and owner of Nyxeos Consulting

Introduction: Knee osteoarthritis (OA) is a common painful disorder. Intra-articular (IA) corticosteroid injections are frequently prescribed to treat knee pain. Lorecivivint (LOR), a novel IA cdc2-Like Kinase (CLK)/Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase (DYRK) inhibitor thought to modulate Wnt and inflammatory pathways, has appeared safe and demonstrated improved patient-reported outcomes compared with placebo. While LOR is proposed for stand-alone use, in clinical practice, providers might administer LOR in close time proximity to IA corticosteroid. This open-label, parallel-arm, healthy volunteer study assessed potential short-term safety, tolerability and pharmacokinetic (PK) interactions between IA LOR and triamcinolone acetonide (TCA) administered 7 days apart., Methods: Healthy volunteers were randomized to Treatment Sequence 1 (IA 40 mg TCA followed by IA 0.07 mg LOR) or Treatment Sequence 2 (IA 0.07 mg LOR followed by IA 40 mg TCA). Treatment-emergent adverse events (TEAEs) were categorized by "epoch", with epoch 1 spanning from first until second injection, and epoch 2 spanning from second injection until end of study. Plasma PK was assessed pre injection and out to 22 days after to assess PK treatment interaction., Results: A total of 18 TEAEs were reported by 11 (27.5%) of 40 enrolled participants, and there were no serious adverse events. Thirteen TEAEs were reported in Treatment Sequence 1 and five in Treatment Sequence 2, similarly distributed between epochs 1 and 2. In all participants and at all time points, plasma LOR concentrations were below the limit of quantification (0.100 ng/mL). Geometric mean concentrations and PK parameters for TCA were similar between treatment sequences., Conclusion: No safety signals were observed. There were no quantifiable plasma concentrations of LOR in either Treatment Sequence. The PK of TCA was unaffected by previous LOR injection. These results suggest that IA administration of LOR and TCA in close time proximity is unlikely to pose a safety concern., Trial Registration: ClinicalTrials.gov identifier, NCT04598542., (© 2023. The Author(s).)

Purpose: The purpose of this study was to report the findings of a hyperreflective nodular epiretinal gliosis observed with optical coherence tomography presumed to be due to subclinical hyaloidal traction causing Mϋller cell cone gliosis., Methods: Retrospective, observational case series., Results: Six eyes of six patients (mean age: 57 years, range 35-81 years) presented with a nodular epiretinal gliosis and had an average follow-up interval of 26 months (range 1-82 months). The mean baseline best-corrected visual acuity was 0.25 ± 0.17 (Snellen equivalent 20/38.3 ± 16.9). Fundus photography demonstrated a yellowish lesion overlying the fovea. Optical coherence tomography imaging revealed a hyperreflective preretinal lesion with a mean vertical length of 267 μ m (range 185-497) and a mean greatest linear diameter of 312 µ m (range 124-640). There was no vitreoretinal abnormality including vitreomacular traction or epiretinal membrane noted in any eye, and two of six eyes displayed a definitive posterior vitreous detachment. These nodules may have occurred before and persisted even after a posterior vitreous detachment or may have been acquired after the posterior vitreous detachment. The nodules typically remained stable with minimal change although in one eye, a posterior vitreous detachment occurred 6 months after initial presentation and lifted the gliosis off of the retinal surface where it remained attached to the posterior hyaloid., Conclusion: Foveal nodular epiretinal gliosis may occur due to subclinical hyaloidal traction on the Müller cell cone even without obvious vitreoretinal interface abnormality on optical coherence tomography.

Purpose: To report the outcomes of pars plana vitrectomy for vitreous hemorrhage (VH) associated with retinal vein occlusion and to identify prognostic indicators., Methods: Interventional, retrospective consecutive case series between 2015 and 2021., Results: The study included 138 eyes of 138 patients (64 female and 74 male); 81 patients had branch retinal vein occlusion and 57 had central retinal vein occlusion. The mean age was 69.8 years. The mean duration between the diagnosis of VH and surgery was 79.6 ± 115.3 (range, 1-572) days. The mean follow-up was 27.2 months. The logarithm of the minimum angle of resolution visual acuity significantly improved from 1.95 ± 0.72 (Snellen equivalent, 20/1782) to 0.99 ± 0.87 (20/195) at 6 months and to 1.06 ± 0.96 (20/230) at the final visit (both P < 0.001). The visual acuity at 6 months improved by three or more lines in 103 eyes (75%). Postoperative complications during follow-up included recurrent VH in 16 eyes (12%) (of which 8 eyes underwent reoperations), rhegmatogenous retinal detachment in six eyes (4%), and new neovascular glaucoma in three eyes (2%). Worse final visual acuity was significantly associated with older age ( P = 0.007), concurrent neovascular glaucoma ( P < 0.001), central retinal vein occlusion ( P < 0.001), worse preoperative visual acuity ( P < 0.001), postoperative new neovascular glaucoma ( P = 0.021), and postoperative retinal detachment ( P < 0.001). The duration of VH was not associated with visual outcomes ( P = 0.684). Preoperative antivascular endothelial growth factor injections and tamponade did not prevent postoperative recurrent VH., Conclusion: Pars plana vitrectomy is effective for VH associated with retinal vein occlusion, regardless of the duration of hemorrhage. However, pre-existing risk factors and postoperative sequelae may limit visual recovery.

Aims: To address the need for noninvasive alternatives to metabolic surgery or duodenal exclusion devices for the management of type 2 diabetes (T2D) and obesity by developing an orally administered therapeutic polymer, GLY-200, designed to bind to and enhance the barrier function of mucus in the gastrointestinal tract to establish duodenal exclusion noninvasively., Materials and Methods: A Phase 1, randomized, double-blind, placebo-controlled, single- (SAD) and multiple-ascending-dose (MAD) healthy volunteer study was conducted. In the SAD arm, four cohorts received a single dose of 0.5 g up to 6.0 g GLY-200 or placebo, while in the MAD arm, four cohorts received 5 days of twice-daily or three-times-daily dosing (total daily dose 2.0 g up to 6.0 g GLY-200 or placebo). Assessments included safety and tolerability (primary) and exploratory pharmacodynamics, including serum glucose, insulin, bile acids and gut hormones., Results: No safety signals were observed; tolerability signals were limited to mild to moderate dose-dependent gastrointestinal events. In the MAD arm (Day 5), reductions in glucose and insulin and increases in bile acids, glucagon-like peptide-1, peptide YY and glicentin, were observed following a nonstandardized meal in subjects receiving twice-daily dosing of 2.0 g GLY-200 (N = 9) versus those receiving placebo (N = 8)., Conclusions: GLY-200 is safe and generally well tolerated at doses of ≤2.0 g twice daily. Pharmacodynamic results mimic the biomarker signature observed after Roux-en-Y gastric bypass and duodenal exclusion devices, indicating a pharmacological effect in the proximal small intestine. This study represents the first clinical demonstration that duodenal exclusion can be achieved with an oral drug and supports further development of GLY-200 for the treatment of obesity and/or T2D., (© 2023 Glyscend Therapeutics. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: To compare 2 mg intravitreal triamcinolone (IVT) versus 40 mg posterior sub-Tenon triamcinolone acetonide (STT) for the treatment of eyes with pseudophakic cystoid macular edema., Methods: A retrospective, single-center review of eyes receiving 2 mg IVT between 3/1/2012-3/1/2017 and 40 mg STT between 1/1/2015-3/1/2017. Visual acuity (VA) and central macular thickness (CMT) were recorded at baseline, 1-, 3-, and 6-month follow-up visits., Results: Forty-five eyes were included in the IVT group and 50 eyes in the STT group. Change in VA from baseline to 1, 3, and 6 months was not significantly different between IVT and STT (6 months: 2.3 lines vs. 2.4 lines, p = .10). The IVT group achieved significantly better CMT improvement from baseline compared to STT at 1 month (255 μm vs. 187 μm; p = .03), but this difference was not present at month 3 (214 μm vs. 212 μm; p = .79) or month 6 (176 μm vs. 207 μm; p = .29). During the 6-month follow-up period, approximately 7% of eyes in the IVT group and 12% of eyes in the STT group developed ocular hypertension ( p = .43), and all cases were successfully managed with topical anti-ocular hypertensive therapy or observation., Conclusions: 2 mg IVT and 40 mg STT both achieved significant improvement in vision and CMT with no significant difference between interventions at 3- and 6-month follow-up.

Purpose: To evaluate patient-reported visual function after ocriplasmin through the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) in patients with symptomatic vitreomacular adhesion/vitreomacular traction including macular hole., Methods: This was a prespecified analysis of a secondary endpoint from the OASIS trial. Patients received a single intravitreal injection of ocriplasmin (0.125 mg) or sham and completed the VFQ-25 questionnaire at baseline and at Months 6, 12, and 24. Clinically meaningful (≥5-point) changes from baseline were assessed., Results: Of the 220 patients enrolled, 146 received ocriplasmin and 74 received sham. At Month 24, the percentage of patients with a ≥5-point improvement from baseline in VFQ-25 composite scores was higher with ocriplasmin versus sham (51.4% vs. 30.1%, 95% confidence interval, 8.1-34.5, P = 0.003). The percentage of patients with ≥5-point worsening at Month 24 was lower with ocriplasmin versus sham (9.5% vs. 15.6%, 95% confidence interval: -15.6 to 3.5, P = 0.191). A larger percentage of patients treated with ocriplasmin versus sham experienced a ≥5-point improvement in VFQ-25 composite and subscale scores at Month 24 regardless of baseline full-thickness macular hole status., Conclusion: A larger percentage of patients with symptomatic vitreomacular adhesion/vitreomacular traction reported clinically meaningful improvements in self-assessed visual function with ocriplasmin than sham.

Purpose: To compare anatomic and functional outcomes in eyes with proliferative diabetic retinopathy (PDR) that were lost to follow-up (LTFU) for more than 6 months after treatment with either intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents or panretinal photocoagulation (PRP)., Design: Retrospective cohort study., Participants: Fifty-nine patients who were LTFU immediately after treatment for more than 6 months between September 2013 and September 2016., Methods: Patients with eyes receiving either intravitreal anti-VEGF treatment or PRP with the next follow-up visit occurring more than 6 months after treatment were identified. Visual acuity (VA) and anatomic outcomes at the visit before being LTFU, the return visit, the 6-month visit after return, the 12-month visit after return, and the final visit were gathered and compared between the 2 treatment groups., Main Outcomes Measures: Visual acuity and anatomic outcomes., Results: Seventy-six eyes of 59 patients were included in the study, of which 30 received IVI with anti-VEGF and 46 received PRP. In the anti-VEGF group, mean VA worsened significantly when comparing the visit before being LTFU (0.43±0.38 logarithm of the minimum angle of resolution [logMAR]) with the return visit (0.97±0.80 logMAR; P = 0.001) as well as with the final visit (0.92±0.94 logMAR; P = 0.01). In the PRP group, mean VA worsened significantly when comparing the visit before being LTFU (0.42±0.34 logMAR) with the return visit (0.62±0.64 logMAR; P = 0.03). However, no significant difference was observed at the final visit (0.46±0.47 logMAR; P = 0.38). There was a significantly greater number of eyes with tractional retinal detachment in the IVI group compared with the PRP group at the final visit (10 vs. 1, respectively; P = 0.005). There was a significantly greater incidence of neovascularization of the iris in the IVI arm compared with the PRP arm at the final visit (4 vs. 0, respectively; P = 0.02)., Conclusions: Eyes with PDR that received only intravitreal anti-VEGF demonstrated worse anatomic and functional outcomes after being LTFU compared with eyes that received PRP. Given the potential sequelae of being LTFU, the choice of treatment for PDR must be considered carefully., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine rates of acute infectious endophthalmitis after pars plana vitrectomy (PPV) in eyes that received intraoperative subconjunctival antibiotics versus eyes that did not., Methods: A retrospective, nonrandomized, comparative case series of 18,886 consecutive cases of transconjunctival 23-, 25-, and 27-gauge PPV over a 5-year period was performed. The impact of prophylactic intraoperative subconjunctival antibiotics on the development of acute infectious postoperative endophthalmitis was examined., Results: Of 18,886 cases of PPV, 14,068 (74.5%) received intraoperative subconjunctival antibiotics, whereas 4,818 (25.5%) did not. Sixteen cases (0.085%, 1/1,176) of post-PPV endophthalmitis were identified. The incidence of endophthalmitis in eyes that received subconjunctival antibiotics was 0.078% (11/14,068 cases, 1/1,282), whereas the incidence in those that did not receive subconjunctival antibiotics was 0.10% (5/4,818 cases, 1/1,000). No statistically significant difference was identified in the incidence of endophthalmitis between those that received subconjunctival antibiotics and those that did not (P = 0.598). Microbial culture was performed in 11 cases with 6 culture-positive cases (5/8 cases that received subconjunctival antibiotics and 1/3 cases that did not)., Conclusion: Prophylactic subconjunctival antibiotics were not associated with a significantly reduced rate of post-PPV endophthalmitis. With consideration of emerging multidrug-resistant bacteria, routine prophylactic subconjunctival antibiotics may not be justified.

Purpose: To evaluate the safety and effects of oral eplerenone in chronic central serous chorioretinopathy., Methods: Prospective, randomized, double-blind, placebo-control study at a tertiary referral academic private practice. For a diagnosis of chronic central serous chorioretinopathy, patients must have had at least 3 months clinical follow-up demonstrating persistent symptoms, subfoveal fluid on spectral-domain optical coherence tomography, and <50% reduction in fluid thickness. Patients were randomized 2:1 (treatment:placebo) to receive eplerenone (25 mg daily for 1 week, then up to 50 mg daily for 8 weeks) or placebo once daily., Results: Fifteen patients completed the study. Ten patients (15 eyes) were randomized into the eplerenone treatment arm, while the remaining 5 patients (6 eyes) received placebo. After 9 weeks of eplerenone therapy, mean logarithm of the minimal angle of resolution visual acuity improved from 0.394 (Snellen equivalent: 20/50) to 0.330 (20/43, P = 0.04). In the placebo group, the mean logarithm of the minimal angle of resolution visual acuity slightly decreased from 0.313 (20/41) to 0.342 (20/44) during the same period (P = 0.21). With respect to anatomic changes, mean maximal subretinal fluid height in the eplerenone group improved from 139.3 μm at baseline to 51.8 μm (P = 0.02), mean subfoveal fluid height improved from 121.4 μm to 29.4 μm (P = 0.01), and mean central subfield thickness improved from 366.2 μm to 283.7 μm (P = 0.02). In comparison with the placebo group, mean maximal subretinal fluid height worsened from 135.9 μm to 172.3 μm (P = 0.32), mean subfoveal fluid height worsened from 92.1 μm to 134.0 μm (P = 0.54), and mean central subfield thickness worsened from 345.0 μm to 380.0 μm (P = 0.37). No patients in either group experienced serious adverse events to result in treatment discontinuation., Conclusion: These findings suggest that oral eplerenone therapy is safe and potentially effective in the treatment of chronic central serous chorioretinopathy with persistent subretinal fluid.

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine., (© 2017 by the American Diabetes Association.)

Importance: There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti-vascular endothelial growth factor (VEGF) injections., Objective: To evaluate the effect of topical dorzolamide hydrochloride-timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy., Design, Setting, and Participants: An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit., Interventions: Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study., Main Outcomes and Measures: Change in central subfield thickness was the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures., Results: Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μm at enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μm at enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μm at enrollment to 239.9 μm at the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60)., Conclusions and Relevance: These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

Background and Objective: This review compares 23-gauge pars plana vitrectomy (PPV) alone versus combined 23-gauge pars plana vitrectomy and scleral buckle (PPV/SB) for primary repair of pseudophakic rhegmatogenous retinal detachment (RRD)., Patients and Methods: A retrospective review of 70 eyes that underwent 23-gauge PPV and 43 eyes that received 23-gauge PPV/SB for pseudophakic RRD. Minimum follow-up was 3 months. Outcome measures included anatomical success, visual acuity, and complication rates., Results: The 23-gauge PPV group achieved primary anatomical success in 58 of 70 cases (83%). Primary success in the PPV/SB group occurred in 36 of 43 cases (84%). Final anatomical success was achieved in all 113 cases (100%). The difference in primary success rates was not statistically significant (P = 1.000, Fisher exact test). Average visual acuity for macula-on RRDs in the PPV group showed a +0.07 logMAR improvement (P = .580) versus a +1.34 improvement (P < .001) in macula-off PPV cases. SB/PPV macula-on cases showed a decrease in logMAR visual acuity by -0.06 (P = .380) while macula-off SB/PPV cases improved by +1.28 (P = .002). There were no significant complications in either group., Conclusion: Both 23-gauge PPV and PPV/SB are effective procedures for repairing pseudophakic RRD and exhibit similar rates of success., (Copyright 2015, SLACK Incorporated.)

Background and Objective: To evaluate the effect of oral eplerenone on subretinal fluid, visual acuity, and choroidal thickness in patients with chronic central serous chorioretinopathy (CSCR)., Patients and Methods: Retrospective review of all patients (14 eyes of 14 patients) monitored for a minimum of 3 months with chronic CSCR who were treated with oral eplerenone in a single multi-physician retina practice. Visual acuity, dilated funduscopic examination, and spectral-domain ocular coherence tomography (OCT) with enhanced depth imaging (EDI) were obtained at each visit. Measurement of subfoveal fluid (SFF) height and choroidal thickness were performed. Two-tailed paired t test was used to calculate statistical significance of pre- and post-treatment variables., Results: At 1 month, 10 of 14 eyes had decreased SFF height on OCT and two eyes had complete resolution of SFF. Mean SFF height decreased from 130 µm to 62 µm (P = .05). Mean choroidal thickness decreased from 315 µm to 282 µm (P = .07). Mean visual acuity improved from logMAR 0.41 to 0.40. At 3 months, 13 of 14 (93%) had decreased SFF on OCT, and nine eyes (64%) had complete resolution of SFF. Mean SFF height decreased to 21 µm (P = .004). Mean choroidal thickness decreased to 253 µm (P = .10). Mean visual acuity improved to logMAR 0.28 (P = .02)., Conclusion: Oral eplerenone may be effective in treating patients with chronic CSCR., (Copyright 2015, SLACK Incorporated.)

Purpose: To describe an alternative technique for avoiding contact with the lids and eyelashes without the use of a metal lid speculum along with the results in clinical practice., Methods: Retrospective review of the medical records of all patients undergoing intravitreal injections of bevacizumab and ranibizumab with lid retraction achieved by bimanual assisted eyelid retraction between November 2010 and December 2011., Results: A total of 10,164 consecutive intravitreal injections were performed, of which 3,834 were bevacizumab and 6,330 were ranibizumab. In this cohort of patients, 3 suspected cases of endophthalmitis developed (2 culture-negative), corresponding to a rate of 0.03%., Conclusion: The technique of bimanual assisted eyelid retraction for intravitreal injection has a low rate of infection similar to the reported rates using a metal lid speculum.

Objectives: To evaluate the effects of high-dose oral omega-3 fatty acid supplementation on electroretinography and omega-3 index in patients with dry age-related macular degeneration., Design: Single institution, prospective, nonrandomized, noncomparative interventional case series comprising 34 eyes of 17 patients older than 50 years of age with early to intermediate age-related macular degeneration. Patients received oral supplementation with 4 g of omega-3 fatty acids daily (840 mg eicosapentaenoic acid/2520 mg docosahexaenoic acid) for 6 months. The main outcome measures included Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, change in N1 and P1 peak amplitudes on multifocal electroretinographic testing, and change in serum omega-3 index., Results: Mean baseline Early Treatment Diabetic Retinopathy Study best-corrected visual acuity letter score was 77 letters (Snellen equivalent of 20/32). There were no statistically significant changes in visual acuity (P = .12) or retinal function by multifocal electroretinographic testing. Serum omega-3 index increased by an average of 7.6% during the course of the study (P < .001). Study limitations included the relatively short duration of the study and small number of participants., Conclusions: Short-term supplementation with high doses of omega-3 fatty acids does not result in any measurable changes in visual acuity or retinal function by multifocal electroretinographic testing. Dietary supplementation with 4 g of omega-3 fatty acids results in a significant increase in serum omega-3 index in patients with dry age-related macular degeneration and may provide a useful clinical measure for future studies., Trial Registration: clinicaltrials.gov Identifier: NCT01258335.

Purpose: To describe a series of 4 patients with Waldenström macroglobulinemia and serous macular detachment, and propose a mechanism for development of subretinal fluid based on optical coherence tomography (OCT) findings., Design: Retrospective observational case series., Methods: The records of patients with Waldenström macroglobulinemia and OCT documentation of serous macular detachment at Wills Eye Institute were reviewed. Data collection included clinical examination, as well as findings on fluorescein angiography (FA) and OCT., Results: Four patients (8 eyes) with Waldenström macroglobulinemia and serous retinal detachment were identified. All eyes had varying degrees of venous stasis retinopathy and intraretinal edema overlying the macular detachment. Three patients had no FA leakage, while 1 patient had macular leakage in a petaloid pattern. Focal outer retinal defects within the detached retina were seen in 4 eyes on OCT imaging. In one eye, development of cystoid macular edema was observed before the outer retinal defect and serous macular detachment. All patients with serous macular detachment had some degree of outer retinal disruption., Conclusion: Discontinuity of the outer retina within the macular detachment may enable immunoglobulins along with accumulated intraretinal fluid to flow into the subretinal space, creating a serous retinal detachment. Even with systemic treatment of the underlying Waldenström macroglobulinemia, the visual prognosis was guarded., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Glucagon-like peptide-1 (GLP-1), a gut-derived hormone secreted in response to nutrients, has several glucose and weight regulating actions including enhancement of glucose-stimulated insulin secretion, suppression of glucagon secretion, slowing of gastric emptying and reduction in food intake. Because of these multiple effects, the GLP-1 receptor system has become an attractive target for type 2 diabetes therapies. However, GLP-1 has significant limitations as a therapeutic due to its rapid degradation (plasma half-life of 1-2 min) by dipeptidyl peptidase-4 (DPP-4). Two main classes of GLP-1-mediated therapies are now in use: DPP-4 inhibitors that reduce the degradation of GLP-1 and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists. The GLP-1R agonists can be further divided into short- and long-acting formulations which have differential effects on their mechanisms of action, ultimately resulting in differential effects on their fasting and postprandial glucose lowering potential. This review summarizes the similarities and differences among DPP-4 inhibitors, short-acting GLP-1R agonists and long-acting GLP-1R agonists. We propose that these different GLP-1-mediated therapies are all necessary tools for the treatment of type 2 diabetes and that the choice of which one to use should depend on the specific needs of the patient. This is analogous to the current use of modern insulins, as short-, intermediate- and long-acting versions are all used to optimize the 24-h plasma glucose profile as needed. Given that GLP-1-mediated therapies have advantages over insulins in terms of hypoglycaemic risk and weight gain, optimized use of these compounds could represent a significant paradigm shift for the treatment of type 2 diabetes., (© 2012 Blackwell Publishing Ltd.)

Aims: Antibody formation to therapeutic peptides is common. This analysis characterizes the time-course and cross-reactivity of anti-exenatide antibodies and potential effects on efficacy and safety., Methods: Data from intent-to-treat patients in 12 controlled (n = 2225,12-52 weeks) and 5 uncontrolled (n = 1538, up to 3 years) exenatide twice-daily (BID) trials and 4 controlled (n = 653,24-30 weeks) exenatide once weekly (QW) trials with 1 uncontrolled period (n = 128,52 weeks) were analysed., Results: Mean titres peaked early (6-22 weeks) and subsequently declined. At 30 weeks, 36.7% of exenatide BID patients were antibody-positive; 31.7% exhibited low titres (≤125) and 5.0% had higher titres (≥625). Antibody incidence declined to 16.9% (1.4% higher titre) at 3 years. Similarly, 56.8% of exenatide QW patients were antibody-positive (45.0% low/11.8% higher titre) at 24-30 weeks, declining to 45.4% positive (9.2% higher titre) at 52 weeks. Treatment-emergent anti-exenatide antibodies from a subset of patients tested did not cross-react with human GLP-1 or glucagon. Other than injection-site reactions, adverse event rates in antibody-positive and antibody-negative patients were similar. Efficacy was robust in both antibody-negative and antibody-positive patients (mean HbA1c change: -1.0 and -0.9%, respectively, exenatide BID; -1.6% and -1.3% exenatide QW). No correlation between change in HbA1c and titre was observed for exenatide BID, although mean reductions were attenuated in the small subset of patients (5%) with higher titres. A significant correlation was observed for exenatide QW with no difference between antibody-negative and low-titre patients, but an attenuated mean reduction in the subset of patients (12%) with higher titres., Conclusions: Low-titre anti-exenatide antibodies were common with exenatide treatment (32% exenatide BID, 45% exenatide QW patients), but had no apparent effect on efficacy. Higher-titre antibodies were less common (5% exenatide BID, 12% exenatide QW) and within that titre group, increasing antibody titre was associated with reduced average efficacy that was statistically significant for exenatide QW. Other than injection-site reactions, anti-exenatide antibodies did not impact the safety of exenatide., (© 2012 Blackwell Publishing Ltd.)

Background and Objective: To assess the safety and efficacy of ranibizumab in patients who had inadequate response to pegaptanib or bevacizumab., Patients and Methods: In this single-center study, 19 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) previously treated with pegaptanib (n = 1), bevacizumab (n = 13), or both (n = 5) received 12 monthly ranibizumab injections (0.5 mg). Outcomes were measured from start of previous therapy (baseline) to start of ranibizumab treatment (day 0) through 12 months., Results: No drug- or injection-related adverse events and no serious adverse events were reported. At 6 and 12 months, 4 and 5 patients gained 3 or more lines of VA, respectively; 3 patients lost less than 3 lines of VA at 6 months, and 6 patients lost less than 3 lines at 12 months. At 6 and 12 months, VA increased by a mean (± standard error of the mean) of 2.06 ± 1.23 and 1.17 ± 0.62 lines, respectively. Central retinal thickness decreased by a mean of 62.65 ± 22.46 and 62.16 ± 29.20 μm at months 6 and 12, respectively. When stratified by pigment epithelial detachment (PED) status, patients without PED had better visual and anatomical outcomes than patients with PED., Conclusion: Ranibizumab has favorable safety and efficacy profiles for patients with AMD without previous response to pegaptanib or bevacizumab., (Copyright 2012, SLACK Incorporated.)

Purpose: To compare intraocular pressure (IOP) and rates of postoperative hypotony with 25-gauge pars plana vitrectomy (PPV) without tamponade using oblique versus direct cannula insertions., Methods: A prospective consecutive series of eyes that underwent 25-gauge PPV without tamponade using an oblique cannula insertion technique was compared with a historical consecutive series of eyes that underwent 25-gauge PPV without tamponade using direct cannula insertions. IOP was recorded before surgery, on postoperative day 1, and on postoperative week 1., Results: Ninety-five eyes had 25-gauge PPV without tamponade, 55 with oblique cannula insertions and 40 with direct insertions. With oblique insertions, there was no statistically significant difference between mean IOPs measured before surgery, on postoperative day 1, and on postoperative week 1. Only 1 (1.8%) of the 55 eyes had hypotony (IOP,

Purpose: To describe two cases of sterile endophthalmitis following intravitreal injection of preservative-free triamcinolone acetonide., Methods: Chart review., Results: Two patients with histories of sterile inflammatory reaction to intravitreal Kenalog (triamcinolone acetonide) subsequently were treated with intravitreal injections of preservative-free triamcinolone. Both patients presented 2 to 3 days after injection with significant anterior chamber cell reaction without pain or inflammation-related conjunctival injection. The intraocular inflammation of both patients resolved completely using only topical steroids and antibiotics., Conclusions: An inflammatory reaction to the vehicle has been the leading hypothesis for the etiology of the sterile inflammatory response following intravitreal Kenalog injections. The use of preservative-free triamcinolone is intended to eliminate this potential source of toxicity. These cases demonstrate that noninfectious endophthalmitis can develop even with preservative-free triamcinolone.

Purpose: To investigate the short-term outcomes of 25-gauge pars plana vitrectomy (PPV) in 18 cases of complicated retinal detachment requiring silicone oil tamponade., Methods: In this retrospective noncomparative review, the primary outcome measures included postoperative anatomical status, preoperative and postoperative visual acuity and intraocular pressure (IOP), cataract progression, development of keratopathy, and other complications. The average follow-up was 5 months (142 days)., Results: Thirteen (72.2%) of 18 patients had attachment postoperatively. There was no difference between preoperative visual acuity and visual acuity at the end of follow-up (P = 0.851). One patient (5.6%) who underwent concomitant penetrating keratoplasty had hypotony (IOP, <6 mmHg) postoperatively and until the end of follow-up. Ocular hypertension in two patients was controlled with antiglaucoma drops. Five (55.6%) of 9 patients who were initially phakic underwent cataract extraction or had documented cataract progression. There were no cases of keratopathy or endophthalmitis. Four patients had intraocular or retinal hemorrhage. Two patients developed significant macular epiretinal membranes, and one developed a parafoveal hole., Conclusions: Sutureless 25-gauge PPV with silicone oil is a relatively safe and comparable alternative to 20-gauge PPV with silicone oil for repair of complicated retinal detachment.

Purpose: To describe the effects of intravitreal bevacizumab in eyes with macular edema resulting from central retinal vein occlusions (CRVO)., Methods: Retrospective consecutive case series of patients diagnosed with macular edema from CRVO who received intravitreal bevacizumab., Results: Thirty eyes of 29 patients with an average age of 72 years (range, 54-87 years) had intravitreal bevacizumab injections. Mean follow-up was 18.1 weeks. Initial mean visual acuity was 20/394. At the 1- and 2-month follow-up, mean visual acuity improved to 20/237 (n = 26, P = 0.04) and 20/187 (n = 21, P = 0.008), respectively. At the 3- and 4-month follow-up, visual acuity improved from 20/228 to 20/157 (n = 15, P = 0.05) and from 20/313 to 20/213 (n = 11, P = 0.03), respectively. No significant changes in visual acuity were found after 4 months though the number of patients in this group was small. Duration of treatment effect following an injection appears to be limited to 2 months for most patients. No ocular or systemic adverse reactions were noted., Conclusions: The visual benefits of intravitreal bevacizumab for macular edema due to CRVO are apparent early but are not sustained without repeated injections. Larger clinical studies with long-term follow-up will be necessary to better elicit the best regimen for this therapy.

Background and Objective: To evaluate the use of intravitreal pegaptanib in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD) in treatment-naive patients., Patients and Methods: In a consecu-tive, retrospective case series, treatment-naïve patients with exudative AMD were treated with intravitreal pegaptanib. Intravitreal injections were typically given every 6 weeks at the discretion of the treating physician. Snellen visual acuity (VA), clinical course, and adverse events were monitored. A minimum of three pegaptanib injections were given. Retreatment criteria included persistent submacular fluid, macular edema, new macular hemorrhage, and loss of vision., Results: The average change in VA for all lesions was a loss of 2.9 lines. Fifteen (14%) patients gained more than 3 lines of VA. The average number of in-jections was 4.8. Ninety-two of 111 lesions were able to be categorized by size. Sixty-six patients had small lesions (< 4 disc areas) with an average change of -2.0 lines, and 26 had large lesions (> or = 4 disc areas) with an average change of -5.4 lines (P < .02). Patients with larger lesions were at greater risk for severe visual loss (P < .01). The average follow-up was approximately 31 weeks (range: 12 to 82 weeks) after the first injection., Conclusions: Pegaptanib therapy resulted in a 2.9 average line loss in patients when all lesions were considered. Small lesions responded favorably, with 15% of patients gaining more than 3 lines of VA. Larger lesions had an increased risk of progression and poor visual outcome.

As the transition to model-based drug development continues, pharmacometric analysis will have an increasingly important role across the entire life cycle of drug discovery, development, regulatory approval, and commercialization. For this reason, pharmacometrics can--and should--have an integrating function in the transformation to model-based development. This essay describes an approach for formalizing the pharmacometrics process using the disciplines encompassed by enterprise engineering.

Background and Objective: To report postoperative complications in eyes undergoing 25-gauge pars plana vitrectomy (PPV)., Patients and Methods: Seventy consecutive eyes that underwent 25-gauge PPV for various indications, including epiretinal membrane, non-clearing vitreous hemorrhage, and idiopathic macular hole, and had a minimum follow-up of 12 weeks were reviewed retrospectively. Main outcome measures included best-corrected Snellen visual acuity, intraocular pressure (IOP), intraoperative complications, and postoperative complications., Results: The mean visual acuity improved from 20/368 preoperatively to 20/105 postoperatively (P < .00005). Intraoperative complications included retinal tears in 2 eyes (2.9%). Postoperative complications included cataract progression in 17 eyes (42.5%), cystoid macular edema exacerbation in 5 eyes (7.1%), and retinal detachment in 1 eye (1.4%). Postoperative day 1 IOP was statistically lower than preoperative IOP in fluid-filled eyes (P = .031) but not in eyes filled with intravitreal air (P = .30) or gas (P = .52). Sclerotomy sutures were required intraoperatively in 5 eyes (7.1%) and postoperative day 1 hypotony was noted in 4 eyes (5.7%). All of these complications were noted in fluid-filled eyes except for one case of postoperative day 1 hypotony with gas tamponade., Conclusions: Intraoperative and postoperative complications were rare in this series of 25-gauge PPV. Postoperative cataract progression and hypotony were the most common complications. Fluid-filled eyes appear to have a higher risk of wound leakage and postoperative hypotony after 25-gauge PPV than eyes with air or gas tamponade.

Pramlintide, an adjunct treatment to mealtime insulin for patients with type 2 and type 1 diabetes, aids glycemic control by suppressing postprandial glucagon secretion, slowing gastric emptying, and enhancing satiety. Because gastric emptying affects oral medication absorption, this placebo-controlled, single-blind, crossover study examined the absorption of 1000 mg of acetaminophen elixir administered -2, -1, 0, +1, and +2 hours relative to pramlintide (120 microg) or 0 hours relative to placebo in 24 patients with type 2 diabetes. When acetaminophen administration occurred 0, +1, or +2 hours relative to pramlintide, the maximum observed plasma concentration of acetaminophen decreased 14% to 29%, and time to maximum observed plasma concentration increased by 0.8 to 1.2 hours compared with administration 0 hours relative to placebo. Pramlintide treatment slowed but did not alter the extent of acetaminophen absorption (area under the concentration-time curve). No serious adverse events or withdrawals were reported. Oral agents should be administered at least 1 hour before or 2 hours after pramlintide injection if rapid onset of action is required for efficacy.

Purpose: To report the optical coherence tomography (OCT) findings in three patients with acute retinal pigment epitheliitis (ARPE)., Design: Retrospective, observational case series., Methods: The charts of three patients with ARPE were reviewed. Approval from the Institutional Review Board was obtained. Fundus photographs, fluorescein angiograms, and OCT findings were examined., Results: Three healthy, young patients presented with acute unilateral blurred vision. Ophthalmoscopy revealed fine pigment stippling surrounded by haloes of hypopigmentation. Fluorescein angiography demonstrated transmission hyperfluorescence. OCT showed abnormal foveal hyperreflectivity involving the outer nuclear layer and photoreceptors in all cases. Disruption of the retinal pigment epithelium (RPE) was seen in two cases. With resolution, the abnormal hyperreflectivity decreased in thickness., Conclusions: OCT confirms the involvement of the outer neurosensory retina in acute retinal pigment epitheliitis. RPE involvement may be a secondary post-inflammatory response, because one case did not have significant disruption of the RPE.

Purpose: To evaluate pars plana vitrectomy (PPV) versus a combined PPV and scleral buckle (PPV/SB) for repair of noncomplex, pseudophakic retinal detachment., Design: Retrospective, nonrandomized, comparative interventional study., Participants: One hundred fifty-two eyes of 152 patients followed up for a mean of 10 months. The case series included 68 consecutive patients who underwent PPV and 84 consecutive patients who underwent a PPV/SB for primary repair of primary pseudophakic retinal detachment at Wills Eye Hospital between 2002 and 2004., Methods: All primary PPV cases were performed by 2 surgeons who perform primary vitrectomy without regard to location of detachment, number and location of break(s), refractive error, or macula status. All primary PPV/SB were performed by a group of surgeons who solely perform PPV/SB on pseudophakic retinal detachments. All eyes underwent a standard 3-port 20-gauge PPV under wide-field viewing and scleral depression. Endolaser photocoagulation was applied either around the retinal tears or 360 degrees to the vitreous base region followed by gas tamponade. Patients with proliferative vitreoretinopathy grade C or worse were excluded from the study., Main Outcome Measures: (1) Single surgery anatomic success rates, (2) preoperative and postoperative visual acuity, and (3) complications., Results: The single surgery anatomic success rate in the primary PPV group was 63 of 68 eyes (92.6%; 95% confidence interval [CI], 84%-98%) and in the primary PPV/SB group was 79 of 84 eyes (94.0%; 95% CI, 87%-98%). Both groups obtained 100% final reattachment rate. There was no statistically significant difference between the success rates (P = 0.75, Fisher exact test). The PPV group's best-corrected postoperative visual acuity demonstrated a +0.10 logarithm of the minimum angle of resolution improvement over the PPV/SB group (P = 0.07). The PPV group had a smaller incidence of postoperative complications (13/68 patients [19.1%] vs. 27/84 patients [32.1%]; P = 0.10, Fisher exact test)., Conclusions: Primary PPV and PPV/SB seem to have similar efficacy in the repair of a matched group of patients with primary noncomplex pseudophakic retinal detachment. There was no statistically significant difference in complication rate between the 2 groups.

Purpose: To assess the number of laser burns applied to the peripheral retina to treat retinopathy of prematurity (ROP) in a recent population of patients and to compare that number with historical data., Methods: The authors performed a retrospective chart review of all patients treated for ROP within a single practice from 2002-2004. There were 183 eyes from 93 patients. Sufficient data for analysis were available on 112 eyes from 57 patients. Data from these patients were compared to those of patients reported upon in 1991., Results: The average number of laser burns applied to the 112 eyes was 2163. Eyes with zone 1 disease had an average of 3077 spots and those with zone 2 disease had an average of 2072 spots. Greater than three months follow-up was available on 42 eyes from 21 patients. Of those eyes, 90% had complete regression of ROP. In an initial report of laser treatment for ROP by several of the same authors in 1991, the average number of laser burns applied for treatment of ROP was 816. There was a 265% increase in the average number of laser applications from the early study to the present., Conclusion: The data indicate that there has been a trend towards more confluent laser treatment to the avascular zone in ROP.

Purpose: To determine the incidence of significant postoperative intraocular pressure (IOP) elevation and other adverse medical events during the first postoperative day in patients undergoing inpatient vitreoretinal surgery., Design: Noncomparative interventional case series., Participants: Two hundred two consecutive patients were admitted prospectively as inpatients after vitreoretinal surgery (vitrectomy and/or scleral buckling)., Methods: Intraocular pressure was measured preoperatively, 5 to 12 hours postoperatively, and on postoperative day 1. Additionally, pain, nausea, and serious systemic adverse events were monitored., Results: Seventeen patients (8.4%) had a 5- to 12-hour IOP measurement above 29 mmHg. Thirty patients (14.8%) had a postoperative day 1 IOP measurement above 29 mmHg. Three patients (1.5%) required a parenteral narcotic to achieve adequate analgesia. Nine patients (4.5%) utilized a parenteral antiemetic for nausea control. Six patients (3.0%) had a hyperglycemic event. No serious systemic adverse events occurred in the early postoperative period., Conclusions: The incidence of a significant IOP spike or systemic adverse events in the early postoperative period in patients undergoing vitreoretinal surgery is low.

Context: First-phase insulin secretion (within 10 min after a sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion., Objective: The objective of the study was to determine whether exenatide can restore a more normal pattern of insulin secretion in subjects with DM2., Design: Fasted subjects received iv insulin infusion to reach plasma glucose 4.4-5.6 mmol/liter. Subjects received iv exenatide (DM2) or saline (DM2 and healthy volunteers), followed by iv glucose challenge., Patients: Thirteen evaluable DM2 subjects were included in the study: 11 males, two females; age, 56 +/- 7 yr; body mass index, 31.7 +/- 2.4 kg/m2; hemoglobin A1c, 6.6 +/- 0.7% (mean +/- sd) treated with diet/exercise (n = 1), metformin (n = 10), or acarbose (n = 2). Controls included 12 healthy, weight-matched subjects with normal glucose tolerance: nine males, three females; age, 57 +/- 9 yr; and body mass index, 32.0 +/- 3.0 kg/m2., Setting: The study was conducted at an academic hospital., Main Outcome Measures: Plasma insulin, plasma C-peptide, insulin secretion rate (derived by deconvolution), and plasma glucagon were the main outcome measures., Results: DM2 subjects administered saline had diminished first-phase insulin secretion, compared with healthy control subjects. Exenatide-treated DM2 subjects had an insulin secretory pattern similar to healthy subjects in both first (0-10 min) and second (10-180 min) phases after glucose challenge, in contrast to saline-treated DM2 subjects. In exenatide-treated DM2 subjects, the most common adverse event was moderate nausea (two of 13 subjects)., Conclusions: Short-term exposure to exenatide can restore the insulin secretory pattern in response to acute rises in glucose concentrations in DM2 patients who, in the absence of exenatide, do not display a first phase of insulin secretion. Loss of first-phase insulin secretion in DM2 patients may be restored by treatment with exenatide.

Exenatide (exendin-4) is an incretin mimetic with potential antidiabetic activity. This study examined the effects of a continuous subcutaneous (SC) infusion of exenatide (0.2, 0.4, 0.6, or 0.8 microg/kg/day) or placebo (PBO) on glycemic control over 23 h intervals. Twelve subjects with type 2 diabetes treated with metformin and/or diet received 10 infusions (4 exenatide, 6 PBO) on consecutive days. Exenatide was given in a dose-increasing design with at least one placebo infusion between each exenatide infusion, and with meals and a snack provided during the first 14 h of infusion. Plasma exenatide concentrations were dose-proportional. Plasma glucose (4-23 h) was lower in all exenatide arms compared to placebo (p<0.0001). The change in insulin/glucagon ratio and amylin concentrations from pre-infusion to post-infusion was increased (p<0.005, p<0.05, respectively) in the combined exenatide arms, but remained unchanged in the placebo groups. Nausea and vomiting were the most common treatment emergent adverse events. Exenatide infusion also appeared to have positive effects on beta-cell and alpha-cell function as measured by proinsulin/insulin ratios and mean glucagon concentrations. In summary, exenatide lowered plasma glucose during both prandial and fasting states when delivered as a continuous SC infusion over twenty-three hours, suggesting that exenatide can provide day-long glycemic control in patients with type 2 diabetes.