Modified Split-Thickness Corneal Patch Graft for Conjunctival Erosions in Patients With the Port Delivery System Implant: Surgical Technique and Long-Term Outcomes.

Purpose: To describe the surgical technique and long-term outcomes of a modified split-thickness corneal patch grafting for conjunctival erosions that can be seen in patients with the Port Delivery System (PDS) implant. Methods: By way of retrospective review of medical records, this interventional case series identified 2 cases in which modified split-thickness corneal patch grafting was used to repair conjunctival erosion in patients with the PDS implant. Results: The surgical approach involved creating a small opening in the corneal graft over the center of the PDS implant to improve visibility and allow for easier access during subsequent refill-exchange procedures. At the last follow-up of 6.9 years and 5.6 years, there was no recurrence of conjunctival erosions in either patient. The PDS implants remained well covered with the split-thickness corneal graft and had undergone multiple implant refills without complication or difficulty. Conclusions: Modified split-thickness corneal patch grafting with central graft aperture offers another option for long-term successful management of conjunctival erosions in patients with a PDS, especially those who have failed prior repair, by allowing sufficient visibility and access for subsequent refill-exchange procedures.

Prevalence and Dose Dependency Analysis of Pentosan Polysulfate Sodium Maculopathy.

PURPOSE: We describe a retrospective cohort study investigating the prevalence of pentosan polysulfate sodium (PPS) maculopathy in patients with PPS exposure, as well as the relationship between cumulative PPS exposure and the presence of PPS-maculopathy. METHODS: Patients were identified through review of the electronic medical record system. Available diagnostic imaging was reviewed for signs of PPS-maculopathy. Patients were also contacted to determine cumulative exposure. RESULTS: Of the 335 identified eligible patient records, 84 had sufficient diagnostic imaging. Sixteen patients had definitive signs of PPS-maculopathy, 6 had likely signs of PPS-maculopathy, and 62 had no signs. The mean cumulative PPS exposure and standard error of the mean (SEM) for patients with any signs of PPS-maculopathy was 1946.0 g (396.0 g), significantly higher than the mean cumulative PPS exposure for patients without such signs of 782.3 g (105.3 g). No significant difference in BCVA was noted. The odds ratio (OR, 95% confidence interval (95% CI)) of PPS-maculopathy was significantly elevated in patients with cumulative PPS exposures of 1500-2000 g [OR 4.72 (0.856-26.02 95% CI)] and greater than 2000 g [OR 28.33 (2.388-336.1, 95% CI)]. Logistic regression analysis confirmed a positive dose response relationship. CONCLUSIONS: We describe the concerning incidence of PPS-maculopathy in a multispecialty ophthalmology practice's patient population and investigate the dose-dependency of PPS-maculopathy. Patients with PPS-maculopathy were shown to have a higher average exposure to PPS than those without the maculopathy. Patients with cumulative PPS exposures greater than 1500 g were shown to have an increased risk of PPS-maculopathy.

Direct Peritoneal Resuscitation (DPR) Improves Acute Physiology and Chronic Health Evaluation (APACHE) IV and Acute Physiology Score When Used in Damage Control Laparotomies: Prospective Cohort Study on 37 Patients.

INTRODUCTION: Using direct peritoneal resuscitation (DPR) as an adjunct when managing patients undergoing damage control laparotomy (DCL) shows promising results. We report our initial experience in utilizing DPR when managing patients who underwent DCL for emergent surgery at the index operation. MATERIALS AND METHODS: We prospectively collected data on 37 patients between August 2020 to October 2021 who underwent DCL with open abdomens after the index operation and utilized DPR. DPR was performed using peritoneal lavage with DIANEAL PD-2-D 2.5% Ca 3.5 mEq/L at a rate of 400ml/hour. Patients' physiological scores and clinical outcomes were evaluated. RESULTS: 86% required DCL and DPR due to septic abdomen/bowel ischemia. The median (interquartile range [IQR]) age was 62 years (53-70); 62% were male, and median (IQR) body mass index was 30.0kg/m2 (25.5-38.4). On DPR initiation, median (IQR) APACHE-IV score was 48 (33-64) and median (IQR) Acute Physiology Score (APS) was 31 (18-54). After initiation, median (IQR) APACHE-IV score and median (IQR) APS were 39 (21-62) and 19 (11-56), respectively, and both showed significant improvement in survivors (p<0.05). Median (IQR) DPR duration was four days (2-8) and primary abdominal closure was achieved in 30 patients (81%). There were eight mortalities (21.6%) within 30 days postoperatively, of which seven were within 3-24 days due to uncontrolled sepsis/multiple organ failure. The most frequent complication was surgical-site infection recorded in 12 patients (32%). Twenty-four patients (67%) were discharged home/transferred to a rehab center/nursing home. CONCLUSION: DPR application showed significant improvement of APACHE-IV score and APS in patients with peritonitis/septic abdomen.

INTRAVITREAL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO OCULAR HISTOPLASMOSIS: Ten-Year Follow-Up.

PURPOSE: To assess the long-term efficacy of intravitreal antivascular endothelial growth factor injections (IVI), alone or in combination with verteporfin photodynamic therapy (IVI/PDT), for management of choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome (POHS). METHODS: Retrospective, comparative, interventional case series analyzing 82 eyes in 74 patients treated with either IVI or IVI/PDT for presumed ocular histoplasmosis syndrome choroidal neovascularization from January 2006 to January 2021. RESULTS: The average logarithm of the minimum angle of resolution VA in year 5 was 0.40 (20/50) and 0.52 (20/67) for IVI versus IVI/PDT groups, respectively ( P = 0.33), and in year 10 was 0.53 (20/58) and 0.64 (20/86), respectively ( P = 0.50). The average number of annual injections over the first 5 years of follow-up was 3.3 versus 1.7 for IVI versus IVI/PDT groups, respectively ( P < 0.001), and over 10 years was 3.3 versus 1.6, respectively ( P < 0.001). Treatment-free interval of 5 years was reached by 39% versus 60% in IVI versus IVI/PDT groups, respectively ( P = 0.95). CONCLUSION: Our study found both IVI and IVI/PDT to be effective in long-term management of presumed ocular histoplasmosis syndrome choroidal neovascularization, with a fewer number of annual injections and longer treatment-free interval in the combination group. However, given the limitations of a retrospective study, a prospective randomized study is necessary to determine whether the addition of PDT significantly decreases treatment burden.

Outcome of Off-Label AREDS 2 Supplementation for the Treatment of Macular Degeneration in Non-Proliferative Idiopathic Type 2 Macular Telangiectasia.

PURPOSE: To evaluate if off-label Age-Related Eye Disease Study 2 (AREDS2) supplementation prevents visual and anatomical deterioration in non-proliferative Idiopathic Macular Telangiectasia Type 2 (IMT2). PATIENTS AND METHODS: This is a single-center retrospective, comparative study of 82 IMT2 eyes treated with AREDS2 from January 1st, 2013 to January 1st, 2018. The study analysis consisted of a non-comparative arm, which included all AREDS2 eyes, and a comparative arm (27 AREDS2 and 42 untreated eyes) that only included eyes with complete follow-up data. Eyes were evaluated at baseline, 12 and 24 months. Better/worse eye sub-analysis was performed in the comparative study arm. Primary outcomes were best corrected visual acuity (BCVA) and optical coherence tomography (OCT) anatomical characteristics including largest cavitation diameter, central macular thickness (CMT), and length of ellipsoid zone (EZ) loss at 24 months. RESULTS: In the non-comparative arm, AREDS2 eyes showed stable BCVA (0.28 ± 0.18 logMAR at baseline vs 0.26 ± 0.19 logMAR at 24 months; p = 0.35) and OCT anatomical features after 24 months of supplementation. In the comparative arm, BCVA mean difference was greater for untreated eyes at 24 months (-0.09 ± 0.15 vs 0.03 ± 0.11 logMAR; p = <0.001). AREDS2 eyes had decreased cavitary diameter and EZ loss compared to untreated eyes at the study endpoint (p = 0.01 and p = 0.02, respectively). CMT remained stable for both cohorts throughout the study. For better/worse eye analysis, untreated eyes had worse BCVA at 24 months in both better and worse eyes (both p = 0.01). For anatomical outcomes, increases in both EZ loss (p = 0.04) and cavitary diameter (p = 0.001) among untreated eyes were only significant for eyes with worse baseline BCVA. CONCLUSION: Our results suggest that off-label AREDS2 supplementation in non-proliferative IMT2 may prevent anatomical and visual deterioration in a subset of eyes.

Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration?

PURPOSE: To determine whether presence of macular hemorrhage on dilated fundus examination (DFE) or fundus photography influences vision outcomes with OCT-guided pro re nata (PRN) ranibizumab retreatment in patients with neovascular age-related macular degeneration (nAMD), we investigated whether hemorrhage without OCT-detectable fluid impacted vision outcomes. DESIGN: Post hoc analysis of prospectively collected data from the 24-month pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvascular age-related macular degeneration (HARBOR) trial (ClinicalTrials.gov identifier, NCT00891735). PARTICIPANTS: This post hoc analysis examined 1097 patients from the intention-to-treat population of HARBOR. METHODS: Dilated fundus examination and fundus photography were evaluated for hemorrhage, and spectral-domain (SD) OCT images from HARBOR participants were analyzed for macular fluid secondary to macular neovascularization. Agreement between methods was determined for each time point. Visual outcomes were evaluated for 82 patients with evidence of hemorrhage on DFE or fundus photography at 3 months and no evidence of SD-exudative activity requiring retreatment at month 3. MAIN OUTCOME MEASURES: Pooled data from the intention-to-treat population of HARBOR were analyzed for hemorrhage on DFE or fundus photography and exudative activity on SD OCT. A subgroup of PRN patients were analyzed for best-corrected visual acuity gains at 24 months. RESULTS: Most study eyes (89% [973/1095]) showed macular hemorrhages at baseline, declining to 31% (319/1042) at month 3 and stabilizing at 11% (111/989) by month 6 of follow-up. After baseline, exudative activity was detected on SD-OCT in more than 89% of eyes when hemorrhage was present on DFE or fundus photography. Patients not requiring a month 3 PRN ranibizumab injection achieved similar visual gains over 24 months, regardless of month 3 hemorrhage presence versus absence: 9.4 and 8.7 Early Treatment Diabetic Retinopathy Study letter scores, respectively (P = 0.74). CONCLUSIONS: After 3 initial ranibizumab injections, SD-OCT detected nAMD activity in 89% of eyes when hemorrhage was present on fundus photography. Ranibizumab retreatment guided by monthly SD-OCT achieved similar vision gains with or without injection when hemorrhage was present without OCT-detectable fluid. This suggests that macular hemorrhages without OCT-detectable macular fluid may not require treatment and DFE may not be needed at every visit. These conclusions should be confirmed in a prospective randomized trial before firm recommendations regarding clinical practice can be made.

INTRAVITREAL AFLIBERCEPT INJECTION FOR CHOROIDAL NEOVASCULARIZATION DUE TO PRESUMED OCULAR HISTOPLASMOSIS SYNDROME: The HANDLE Study.

PURPOSE: To evaluate intravitreal aflibercept injection (IAI) in patients with presumed ocular histoplasmosis syndrome and choroidal neovascularization. METHODS: Open-label randomized Phase I/II study of IAI in patients with presumed ocular histoplasmosis syndrome-related choroidal neovascularization. Thirty-nine eyes from 39 patients were randomized in a 1:1 ratio to 2 groups. The Sustained Group eyes (n = 19) underwent monthly IAI for 3 months, then mandatory IAI every 2 months for 12 months (with an option for monthly PRN dosing, if needed). The PRN Group eyes (n = 20) received 1 IAI at randomization, then monthly PRN IAI for 12 months. RESULTS: Thirty-nine eyes (19 eyes Sustained Group and 20 eyes PRN Group) were randomized. Average age of participants was 50 years (19-75), with 16 men and 23 women. Ten, 12, and 17 eyes demonstrated extrafoveal, juxtafoveal, and subfoveal choroidal neovascularization, respectively. All eyes in both groups received IAI at baseline, with the Sustained and PRN groups receiving on an average 7.5 (5-11) and 4.6 (1-10) injections, respectively, over the 12 months. At baseline, overall average visual acuity was 68 letters (13-87 letters) with Snellen equivalent of 20/42 (20/20-20/160). At 12-month follow-up, Sustained Group's average visual acuity was 84.9 letters (74-94) and Snellen equivalent was 20/21 (20/13-20/32), indicating an average improvement of 12 letters (6 letters loss to 36 letters gain) (P < 0.01). The PRN Group's 12-month average visual acuity was 80.9 letters (60-94) and Snellen equivalent was 20/26 (20/13-20/63), indicating an average gain of 19 letters (4-75) (P < 0.01). Mean baseline central subfield thickness (CST) was 374 µm and mean 1-year CST was 260 µm (P < 0.01) among all study participants. The Sustained Group's mean baseline CST was 383 µm and mean 12-month CST was 268 µm (P < 0.01). Mean baseline CST of the PRN Group was 360.8 µm, with the final mean CST of 260.5 µm (P < 0.01). No reported endophthalmitis, retinal tears, detachments, vitreous hemorrhage, nor adverse thrombotic events were reported. CONCLUSION: Intravitreal aflibercept resulted in improved visual and anatomical outcomes with a favorable safety profile. PRN IAI dosing required less injections with similar visual and anatomical outcomes compared with sustained dosing.

EVALUATION OF FULL-FIELD ELECTRORETINOGRAM REDUCTIONS AFTER OCRIPLASMIN TREATMENT: Results of the OASIS Trial ERG Substudy.

PURPOSE: To explore a possible association between full-field electroretinograms with vitreomacular adhesion resolution and best-corrected visual acuity as part of the prospective, randomized, double-masked, sham-controlled Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial studying ocriplasmin. METHODS: The ERG substudy enrolled 62 of 220 OASIS subjects (randomized 2:1) and analyzed full-field electroretinograms and their association with both vitreomacular adhesion resolution and best-corrected visual acuity from baseline through Month 24. Electroretinogram reductions were defined as acute full-field electroretinogram reductions in amplitude of ≥40% from baseline occurring at postinjection Day 7 or Day 28. RESULTS: In the ocriplasmin group, 16/40 (40%) subjects developed ERG reductions, compared to 1/21 (4.8%) in the sham group; 13/16 (81.3%) and 1/1 (100%) resolved by study end, respectively. A total of 11/16 (68.8%) ocriplasmin-treated subjects with ERG reductions achieved vitreomacular adhesion resolution, compared to those without (9/24, 37.5%). The ocriplasmin-treated subjects with ERG reductions also gained more letters on average (11.3 vs. 9.3 letters) from baseline and had a difference of 6.7 letters in mean best-corrected visual acuity by study end compared to those without ERG reductions. CONCLUSION: Ocriplasmin-treated subjects with ERG reductions had a higher rate of vitreomacular adhesion resolution and showed better visual improvement than their counterparts without ERG reductions or sham subjects by study end.

Comparison of outcomes: scleral buckling and pars plana vitrectomy versus vitrectomy alone for primary repair of rhegmatogenous retinal detachment.

OBJECTIVE: To assess the combination of scleral buckling (SB) and pars plana vitrectomy (PPV) versus PPV alone in the primary repair of rhegmatogenous retinal detachments (RRDs). METHODS: The current study was a retrospective, comparative, interventional, consecutive case series of 179 eyes of 174 patients who underwent primary RRD repair by five surgeons between January 1, 2008 and December 31, 2010, utilizing SB with PPV or PPV. Univariate and multivariate analyses were used to compare the efficacy of the two surgical strategies and assess for risk factors of proliferative vitreoretinopathy (PVR). RESULTS: Single surgery anatomic success (SSAS) was similar (P=0.76) between the PPV group (112 of 132 eyes, 85%) and SB with PPV group (39 of 47 eyes, 83%). Final anatomic success was 100% in each group. There was no difference in rates of PVR formation (PPV 16% vs SB with PPV 19%, P=0.70). Final logarithm of the minimum angle of resolution acuity was 0.33 (20/43) in the PPV group and 0.37 (20/47) in the SB with PPV group (P=0.62). Postoperative anterior chamber fibrin was highly correlated with PVR formation (PVR 13% vs no PVR 0.7%, P=0.003; odds ratio =68.37, P=0.007). Separate analysis of medium- to high-complexity cases showed similar SSAS (PPV 86% vs SB with PPV 83%, P=0.45). CONCLUSION: SB with PPV versus PPV alone were similarly efficacious for repair of primary RRDs of varying complexity. SSAS rates, PVR incidence, and final visual acuities were not significantly different.

SUBRETINAL CANNULATION AS A COMPLICATION OF SUTURE TRABECULOTOMY SURGERY IN A PEDIATRIC PATIENT.

PURPOSE: To report a case of inadvertent subretinal cannulation of ab externo suture trabeculotomy surgery associated with serous macular detachment. METHODS: Retrospective case report. Ophthalmic examination and portable spectral domain optical coherence tomography (Envisu C2300; Bioptogen, Morrisville, NC) were performed under general anesthesia. RESULTS: A 5-year-old girl with uveitis secondary to oligoarticular juvenile idiopathic arthritis underwent trabeculotomy surgery of the left eye for steroid-induced glaucoma refractory to medical management. The surgery was complicated by inadvertent subretinal cannulation with the prolene suture. Multiple, arcuate, hypopigmented subretinal tracks, originating from the ora serrata, were observed. Spectral domain optical coherence tomography images through the macula revealed subretinal fluid overlying funduscopically visible tracks, defects in photoreceptor outer segments overlying the tracks, and normal choroidal anatomy. The serous macular detachment resolved spontaneously after 4 months and visual acuity returned to baseline 20/25 in the left eye, consistent with reversible localized damage to the outer retina and retinal pigment epithelium. CONCLUSION: We report a case of inadvertent subretinal cannulation during suture trabeculotomy surgery that resulted in serous macular detachment which resolved spontaneously. The inadvertent complication demonstrated a pathway for administration of therapeutics to the subretinal space.

LONG-TERM OUTCOMES OF INTRAVITREAL BEVACIZUMAB THERAPY FOR SUBRETINAL NEOVASCULARIZATION SECONDARY TO IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To assess the long-term visual acuity results for intravitreal bevacizumab therapy in the treatment of subretinal neovascular membrane (SRNVM) secondary to idiopathic macular telangiectasia (Mactel) Type 2. METHODS: This retrospective review of a consecutive, interventional case series includes patients with SRNVM secondary to Mactel Type 2 who were seen at Cincinnati Eye Institute from February 2006 to December 2014. Best-corrected visual acuity, fluorescein angiography, and optical coherence tomography measurements were performed. Exclusion criteria were the following: Mactel Type 2 patients without SRNVM, Mactel Type 1 patients, patients who had SRNVM or macular edema related to other maculopathies, and patients who had pars plana vitrectomy or laser treatment to the macula during the course of care or before their first visit. RESULTS: Twenty-five eyes of 20 patients with SRNVM secondary to Mactel Type 2 were included in the study. The mean baseline best-corrected visual acuity was 20/91 (median: 20/69) and the mean final best-corrected visual acuity was 20/62 (median: 20/60) at the last visit (P < 0.0001). The mean number of injections was 8.4 ± 11.1 (range: 2-53, median: 4). The mean pretreatment central macular thickness of 254 µm improved to 205 µm at the final visit (P = 0.011). No complications related to intravitreal bevacizumab injection were noted during the mean follow-up time of 40.8 ± 33.7 months (range: 4-108 months, median: 24 months). CONCLUSION: Intravitreal bevacizumab therapy is an effective long-term treatment modality for SRNVM secondary to Mactel Type 2 based on improvement in best-corrected visual acuity and associated reduction in central macular thickness.

Outcomes of transconjunctival sutureless 27-gauge vitrectomy with silicone oil infusion.

PURPOSE: To demonstrate the safety and efficacy of 27-gauge pars plana vitrectomy (PPV) in selected patients with vitreoretinal diseases requiring silicone oil (SO) tamponade. METHODS: Retrospective review of a consecutive interventional case series at a single center. RESULTS: Twenty-one eyes of 19 patients were included in the study. The indications for PPV and SO tamponade were as follows: fibrovascular tractional retinal detachment (12 eyes), rhegmatogenous retinal detachment with proliferative vitreoretinopathy (three eyes), primary rhegmatogenous retinal detachment (two eyes), macular hole (two eyes), vitreous hemorrhage (one eye), and endophthalmitis (one eye). All eyes underwent transconjunctival sutureless 27-gauge PPV with either 1000-cS (16 eyes) or 5000-cS (five eyes) SO tamponade. No intraoperative complications occurred. Mean preoperative best-corrected visual acuity (BCVA) was 20/300 (range, light perception to 20/40; median, counting fingers). Mean postoperative BCVA was 20/160 (range, no light perception to 20/25; median 20/300; p = 0.022). Follow-up was 6.4 ± 8.8 months (range, 1-38 months; median, 4 months). No complications relating to 27-gauge placement of SO were observed. CONCLUSIONS: Results show that 27-gauge PPV with SO injection appears safe, is efficient, and may be considered for the surgical management of vitreoretinal diseases requiring SO tamponade.

LONG-TERM RESULTS OF COMBINED AB INTERNO TRABECULOTOMY (TRABECTOME) AND SMALL-GAUGE PARS PLANA VITRECTOMY.

PURPOSE: To report outcomes of patients who have undergone combined Trabectome and pars plana vitrectomy. METHODS: Institutional Review Board-approved retrospective chart review of patients seen at the Cincinnati Eye Institute before January 2014 undergoing combined Trabectome and pars plana vitrectomy for uncontrolled glaucoma and visually significant retina pathology. Charts were reviewed to identify changes in intraocular pressure, visual acuity, and change in glaucoma medication requirement up to 1 year after surgery. RESULTS: Four patients met the inclusion criteria with 12-month follow-up, and two of the patients were male. All patients underwent 25-gauge pars plana vitrectomy and Trabectome surgery. Mean preoperative LogMAR visual acuity was 0.39 (20/49) and 12-month LogMAR visual acuity was 0.21 (20/32) (P = 0.06). Mean preoperative intraocular pressure was 17 mmHg and mean preoperative glaucoma medication requirement was 2.5 topical medications. Twelve-month mean intraocular pressure was 12.8 mmHg (P = 0.07), and mean topical glaucoma medication requirement was 2.3 medications (P = 0.39). All patients were off steroids and anti-inflammatories at the final visit. One patient developed a hyphema requiring anterior chamber washout at 1 week. No other complications occurred. CONCLUSION: The results suggest that combined Trabectome and pars plana vitrectomy seems effective in the management of glaucoma in patients with visually significant retina pathology.

Stability of the acrysof toric intraocular lens in combined cataract surgery and transconjunctival sutureless vitrectomy.

PURPOSE: To report the outcomes of combined cataract surgery with toric intraocular lens (IOL) implantation when performed in conjunction with transconjunctival sutureless pars plana vitrectomy. DESIGN: Retrospective interventional case series. PARTICIPANTS: Consecutive series of 55 eyes of 51 patients from April 2007 to December of 2010. METHODS: All eyes underwent combined simultaneous small incision cataract surgery, toric IOL implantation, and transconjunctival sutureless vitrectomy surgery. MAIN OUTCOME MEASURES: Postoperative visual acuity, postoperative astigmatism, and rotational stability of the IOL. RESULTS: Preoperative best-corrected visual acuity was 0.32 ± 0.15 logMar (Snellen 20/43) and improved to 0.16 ± 0.10 (Snellen 20/29) postoperatively uncorrected (P < 0.01) and to 0.08 ± 0.11 best-corrected (Snellen 20/24) (P < 0.01). Preoperative astigmatism was 1.75 ± 1.0 diopters (D) (range, 0-4.75 D) and improved to 0.5 ± 0.50 D (range, 0-2.5 D) postoperatively (P < 0.01). Final measured postoperative IOL axis deviation from target axis was 4 ± 6° (range, 0-32). Final IOL axis was within 5° of target in 47 (85%) eyes, within 10 degrees of target in 51 (93%) eyes, and was within 15° of target in 52 (95%) eyes. CONCLUSION: Toric lens position and axis remained stable after implantation during combined cataract surgery and transconjunctival sutureless vitrectomy.

Cost comparison of intravitreal aflibercept with bevacizumab and ranibizumab for the treatment of wet age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To test the hypothesis that although intravitreal aflibercept (IVA) is expected to be more expensive, the extra cost of treatment would not result in additional vision gain compared with intravitreal bevacizumab (IVB) for the treatment of wet age-related macular degeneration (AMD). PATIENTS AND METHODS: A retrospective chart review of patients receiving IVB or intravitreal ranibizumab (IVR) who were subsequently changed to IVA for active wet AMD. RESULTS: Thirty-three eyes were included in the study. The mean number of IVB, IVR, and IVA injections per eye over a 6-month period was seven, six, and five, respectively. Visual outcomes were similar in all three groups at the end of the study period. The average drug cost of IVB, IVR, and IVA injections per eye over 6 months was $326, $11,400, and $9,720, respectively. CONCLUSION: Aflibercept may allow a modest extension of the treatment interval, but cost makes IVA an expensive alternative without a visual benefit compared with IVB in patients with active wet AMD.

Treatment of diabetic macular edema with an inhibitor of vascular endothelial-protein tyrosine phosphatase that activates Tie2.

PURPOSE: AKB-9778 is a small-molecule competitive inhibitor of vascular endothelial-protein tyrosine phosphatase (VE-PTP) that promotes Tie2 activation and reduces vascular leakage and neovascularization in mouse models. The purpose of this study was to test the safety, tolerability, pharmacokinetics, and biological activity of AKB-9778 in patients with diabetic macular edema (DME). DESIGN: Open-label, dose-escalation clinical trial. PARTICIPANTS: Four dose cohorts of 6 patients with DME self-administered subcutaneous injections of 5 mg, 15 mg, 22.5 mg, or 30 mg AKB-9778 twice daily for 4 weeks. METHODS: Patients were seen weekly during a 4-week treatment period for safety assessments, best-corrected visual acuity (BCVA) assessment by Early Treatment Diabetic Retinopathy Study protocol, and measurement of central subfield thickness (CST) by spectral-domain optical coherence tomography. Additional safety assessments were performed at 6, 8, and 12 weeks. MAIN OUTCOME MEASURES: Safety assessments, change from baseline BCVA, and change from baseline CST. RESULTS: All doses were well tolerated. A modest, transient reduction in blood pressure and adverse events consistent with vasodilatory activity of AKB-9778 emerged at doses of 22.5 mg or more twice daily. At the week 4 primary end point, BCVA improved 5 letters or more from baseline in 13 of the 18 patients receiving 15 mg or more twice daily; 1 patient improved by 10 to 15 letters, and 2 patients improved by more than 15 letters. Among 18 patients receiving 15 mg or more twice daily, CST decreased by more than 100 µm in 5 patients and by 50 to 100 µm in 2 patients. There was a significant correlation between reduction in CST and improvement in BCVA. CONCLUSIONS: No safety concerns were identified after systemic administration of AKB-9778 for 4 weeks in patients with DME, and doses of 15 mg or more twice daily reduced macular edema and improved vision in some patients. This is a preliminary demonstration of clinical safety and efficacy of a VE-PTP inhibitor and Tie2 activator.