Complications, Compliance, and 3-Year Outcomes After Endolaserless Vitrectomy With Aflibercept Monotherapy for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage.

BACKGROUND AND OBJECTIVE: To report the 3-year outcomes for endolaserless vitrectomy with intravitreal aflibercept injection (IAI) monotherapy for proliferative diabetic retinopathy (PDR)-related vitreous hemorrhage (VH). MATERIALS AND METHOD: Eyes underwent endolaserless vitrectomy and received one preoperative and intraoperative IAI followed by randomization to a q8week or q16week IAI group. Additional IAI was administered as needed. RESULTS: 31/40 eyes were randomized (14 q8week eyes, 17 q16week eyes). Through 152 weeks, q8week and q16week eyes received 18.6 and 12.1 IAI, respectively. Q8week eyes observed a 34 letter visual acuity (VA) increase (P = 0.003) compared to a 27 letter increase in the q16week group (P = 0.013). CONCLUSIONS: Endolaserless vitrectomy with aflibercept monotherapy for PDR-related VH provides significant long-term visual gains. Frequent IAI is required for fewer proliferative consequences. [Ophthalmic Surg Lasers Imaging Retina 2023;54:89-96.].

Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab.

Importance: Anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) favorably affects diabetic retinopathy (DR) improvement and worsening. It is unknown whether these effects differ across anti-VEGF agents. Objective: To compare changes in DR severity during aflibercept, bevacizumab, or ranibizumab treatment for DME. Design, Setting, and Participants: Preplanned secondary analysis of data from a comparative effectiveness trial for center-involved DME was conducted in 650 participants receiving aflibercept, bevacizumab, or ranibizumab. Retinopathy improvement and worsening were determined during 2 years of treatment. Participants were randomized in 2012 through 2013, and the trial concluded on September 23, 2015. Interventions: Random assignment to aflibercept, 2.0 mg; bevacizumab, 1.25 mg; ranibizumab, 0.3 mg, up to every 4 weeks through 2 years following a retreatment protocol. Main Outcomes and Measures: Percentages with retinopathy improvement at 1 and 2 years and cumulative probabilities for retinopathy worsening through 2-year without adjustment for multiple outcomes. Results: A total of 650 participants (495 [76.2%] nonproliferative DR [NPDR], 155 proliferative DR [PDR]) were analyzed; 302 (46.5%) were women and mean (SD) age was 61 (10) years; 425 (65.4%) were white. At 1 year, among 423 NPDR eyes, 44 of 141 (31.2%) treated with aflibercept, 29 of 131 (22.1%) with bevacizumab, and 57 of 151 (37.7%) with ranibizumab had improvement of DR severity (adjusted difference: 11.7%; 95% CI, 2.9% to 20.6%; P = .004 for aflibercept vs bevacizumab; 8.9%; 95% CI, 1.7% to 16.1%; P = .01 for ranibizumab vs bevacizumab; and 2.9%; 95% CI, -5.7% to 11.4%; P = .51 for aflibercept vs ranibizumab). At 2 years, 33 eyes (24.8%) in the aflibercept group, 25 eyes (22.1%) in the bevacizumab group, and 40 eyes (31.0%) in the ranibizumab group had DR improvement; no treatment group differences were identified. For 93 eyes with PDR at baseline, 1-year improvement rates were 75.9% for aflibercept, 31.4% for bevacizumab, and 55.2% for ranibizumab (adjusted difference: 50.4%; 95% CI, 26.8% to 74.0%; P < .001 for aflibercept vs bevacizumab; 20.4%; 95% CI, -3.1% to 44.0%; P = .09 for ranibizumab vs bevacizumab; and 30.0%; 95% CI, 4.4% to 55.6%; P = .02 for aflibercept vs ranibizumab). These rates and treatment group differences appeared to be maintained at 2 years. Despite the reduced numbers of injections in the second year, 66 (59.5%) of NPDR and 28 (70.0%) of PDR eyes that manifested improvement at 1 year maintained improvement at 2 years. Two-year cumulative rates for retinopathy worsening ranged from 7.1% to 10.2% and 17.2% to 26.4% among anti-VEGF groups for NPDR and PDR eyes, respectively. No statistically significant treatment differences were noted. Conclusions and Relevance: At 1 and 2 years, eyes with NPDR receiving anti-VEGF treatment for DME may experience improvement in DR severity. Less improvement was demonstrated with bevacizumab at 1 year than with aflibercept or ranibizumab. Aflibercept was associated with more improvement at 1 and 2 years in the smaller subgroup of participants with PDR at baseline. All 3 anti-VEGF treatments were associated with low rates of DR worsening. These data provide additional outcomes that might be considered when choosing an anti-VEGF agent to treat DME.

Intravitreal Aflibercept for Neovascular Polypoidal Choroidal Vasculopathy in a Predominantly Non-Asian Population: RIVAL Results.

BACKGROUND AND OBJECTIVE: To evaluate safety and efficacy of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) injection (IAI) for the treatment of neovascular polypoidal choroidal vasculopathy (PCV) in a predominantly non-Asian population. PATIENTS AND METHODS: This was an open-label, prospective, unmasked, nonrandomized clinical trial. Twenty eyes with neovascular PCV received monthly 2.0 mg IAI for 3 months followed by mandatory IAI every 2 months for 12 months. RESULTS: The mean change in ETDRS best-corrected visual acuity from baseline to 1 year was +11 letters in the treatment-naïve group, +5 letters in the treatment non-naïve group, and +9 letters overall. There was an overall mean reduction of 70 µm from baseline central subfield thickness (CST) at 1 year. Patients received a mean of 6.2 mandatory and 0.7 additional IAI injections overall during the course of 1 year. No serious ocular adverse events were reported. CONCLUSION: At 1 year, neovascular PCV in a predominantly non-Asian population treated with IAI demonstrated favorable visual, anatomic, and safety outcomes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:34-44.].

Ranibizumab 0.3 mg for Persistent Diabetic Macular Edema After Recent, Frequent, and Chronic Bevacizumab: The ROTATE Trial.

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of 0.3 mg ranibizumab (Lucentis; Genentech, South San Francisco, CA) in eyes with persistent diabetic macular edema (DME) after recent, chronic, and frequent bevacizumab (Avastin; Genentech, South San Francisco, CA). PATIENTS AND METHODS: Open-label, prospective study of 0.3 mg ranibizumab for eyes with persistent DME after bevacizumab. Thirty eyes randomized to a sustained group or a pro re nata (PRN) dosing group. RESULTS: The mean change in ETDRS best-corrected visual acuity from baseline to 1 year was +6.7 letters in the sustained group, +6.4 letters in the PRN group, and +6.5 letters overall. There was an overall mean reduction of 116 µm from baseline central subfield thickness at 1 year, with -92 µm and -127 µm decreases in the sustained and PRN groups, respectively. Adverse events included two deaths; one patient with multiple cardiopulmonary comorbidities, myocardial infarction, stroke, osteomyelitis; and mild posterior subcapsular cataracts in two eyes. CONCLUSION: Ranibizumab 0.3 mg demonstrated improved visual and anatomic outcomes in patients with persistent DME following bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1030-1037.].

Intravitreal ranibizumab for polypoidal choroidal vasculopathy in non-Asian patients.

PURPOSE: To determine safety, tolerability, and efficacy of intravitreal ranibizumab in the treatment of polypoidal choroidal vasculopathy in a non-Asian population. METHODS: Phase I/II, prospective, open-label, single-center, nonrandomized, uncontrolled, consecutive, interventional case series of 20 eyes in 19 patients with exudative active polypoidal choroidal vasculopathy. Eyes received 3 monthly intravitreal ranibizumab injections (0.3 or 0.5 mg), with additional ranibizumab injections, observation, or alternative treatments at investigators' discretion, through 24 months. Main outcome measures were ocular and systemic safety and mean change from baseline in best-corrected visual acuity and center point thickness. RESULTS: Visually significant ocular adverse events included cataract progression (n = 3), mild vitreous hemorrhage (n = 2), and macular hole (n = 1). No systemic drug-related adverse events were observed. Mean baseline best-corrected visual acuity was 20/127 (range, 20/16-20/500) and center point thickness was 298 µm. Mean best-corrected visual acuity increased from baseline by 1.2 Snellen lines at 12 months and 24 months. Mean center point thickness decreased by 53 µm and 67 µm from baseline at 12 months and 24 months, respectively. CONCLUSION: Intravitreal ranibizumab was well tolerated in non-Asian patients with polypoidal choroidal vasculopathy; the majority of eyes experienced improvements in best-corrected visual acuity and center point thickness after ranibizumab treatment.

Formulation and evaluation of domperidone loaded mineral oil entrapped emulsion gel (MOEG) buoyant beads.

Alginate based mineral oil entrapped emulsion gel (MOEG) buoyant beads of domperidone were prepared by emulsion gelation technique. The prepared beads were evaluated for particle size, surface morphology, buoyancy, actual drug content and entrapment efficiency. Effect of different oils (castor oil, olive oil and linseed oil) and oil concentrations (10%, 15% and 20%, w/w) on uniformity, homogeneity and integrity of the beads was also studied. Density of the formulated beads was found to be ranging between 0.101 and 0.182 g/cm3. The results of the in vitro drug release indicated that linseed oil showed to be good release retardant compared to castor oil and olive oil. Moreover, the beads formulated using 15%, w/w linseed oil were more uniform in shape, exhibited maximum buoyancy and minimal oil leakage. Diffusion exponent (n) value varied from 0.4855 to 0.7710 indicating anomalous drug release behavior involving swelling, diffusion and/or erosion of the polymer matrix.

23-gauge vitrectomy in 100 eyes: short-term visual outcomes and complications.

PURPOSE: To report the short-term outcomes and complications of patients undergoing 23-gauge transconjunctival sutureless pars plana vitrectomy. METHODS: Retrospective, consecutive, noncomparative case series in which 100 eyes of 100 patients underwent elective 23-gauge pars plana vitrectomy for a variety of surgical indications. All patients were examined on postoperative day 1 and then approximately 1 and 4 weeks later. Demographic and ophthalmic data were recorded. RESULTS: Fifty-two men and 48 women (mean age = 65 years) were observed for a mean of 26 weeks. Mean preoperative visual acuity was 20/842 and mean final postoperative visual acuity was 20/429. Postoperative visual acuity improved in 68% of patients, worsened in 16%, and remained unchanged in 16%. Mean preoperative intraocular pressure was 15 mmHg and mean postoperative intraocular pressure at final visit was 14 mmHg. No sutures were required to close sclerotomies and no intraoperative complications were observed, though one eye required conversion to 20-gauge pars plana vitrectomy during silicone oil removal. Postoperative complications included retinal detachment, cataract progression, vitreous hemorrhage, persistent macular hole, new macular hole, phthisis, posterior capsular opacification, and severe chemosis. CONCLUSIONS: Twenty-three-gauge pars plana vitrectomy demonstrates short-term visual outcomes and complication rates that are comparable to those reported with 20- and 25-gauge systems.

Vitreal penetration of oral moxifloxacin in humans.

PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral administration. DESIGN: Prospective, nonrandomized clinical series. METHODS: Twenty-four patients (mean age = 62.8 years) undergoing elective pars plana vitrectomy were assigned to a dosing group: control (n = 3), which received no medication; single-dose (n = 11), which received one 400 mg oral dose of moxifloxacin 3 hours before surgery; and five-dose (n = 10), which received one 400 mg dose on each of the 4 days preceding surgery and a fifth dose 3 hours before surgery. Vitreous samples were obtained and analyzed. RESULTS: Control, below quantifiable levels; single-dose, 0.572 +/- 0.239 microg/mL; and five-dose, 1.200 +/- 0.645 microg/mL. CONCLUSIONS: Five doses of oral moxifloxacin lead to higher intravitreal drug concentrations than single-dose administration. Both regimens, however, achieve levels that exceed the MIC90 of many bacteria implicated in postoperative endophthalmitis.

Vitreal penetration of oral and topical moxifloxacin in humans.

PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral and topical administration. DESIGN: Prospective, nonrandomized clinical trial. METHODS: Twenty-four patients were assigned to one of four dosing groups: control (n = 3), which received no medication; oral (n = 8), which received two 400 mg oral doses of moxifloxacin before surgery; topical (n = 8), which received one drop of topical moxifloxacin 0.5% every 15 minutes for the hour preceding surgery; and combined (n = 5), which received two 400 mg oral doses and one drop of topical moxifloxacin 0.5% hourly for 18 hours prior to surgery. Vitreous samples were obtained and analyzed. RESULTS: Control, below quantifiable levels; oral, 1.553 +/- 0.33 microg/ml; topical, 0.027 microg/ml; and combined, 2.219 +/- 0.71 microg/ml. One topical patient developed postoperative endophthalmitis. CONCLUSIONS: In contrast to topical moxifloxacin, oral moxifloxacin achieves significant levels in the noninflamed human vitreous.

Alternative splicing of the APC gene in the neural retina and retinal pigment epithelium.

PURPOSE: Hypertrophy and hyperplasia of the retinal pigment epithelium (RPE) is associated with an inherited predisposition to human familial adenomatous polyposis coli, suggesting that expression of the adenomatous polyposis coli (APC) tumor suppressor may regulate RPE proliferation/differentiation. Distinctive APC isoforms exist in different cell types due to alternative splicing of the APC transcripts. We hypothesize that differences in expression patterns of APC protein isoforms are critical to RPE proliferation/differentiation. METHODS: To investigate these relationships, APC gene expression was characterized in the retinas and RPE from fetal and adult human and mouse, and in the epiretinal membranes (ERM) from 5 patients with proliferative vitreoretinopathy (PVR). Expression patterns of alternative splice-forms of APC transcripts were evaluated by comparative quantitative RT-PCR. Exon 1 of APC encodes a heptad repeat that confers the ability of APC to homodimerize. APC protein isoforms containing or lacking this heptad were characterized by western blot analysis and immunohistochemistry. RESULTS: Comparative quantitative RT-PCR demonstrated a predominant exon 1 containing, conventional APC splice-form in the early developing fetal RPE and retina, and in all the tested ERM samples from patients with PVR. This method also demonstrated an increased level of exon 1 lacking APC splice-form in the mature RPE and retina. Western blot analysis and immunofluorescence microscopy demonstrated the conventional APC only in the RPE, and the APC isoform without the first heptad repeat in both the retina and RPE. Immunofluorescence microscopy also demonstrated only the conventional APC in the ERM samples tested. CONCLUSIONS: These results suggest that alternative splicing of APC leads to differential APC expression with potentially unique functions. APC isoform without the first heptad repeat may play a role in cell cycle cessation in the adult retina and RPE, and the down regulation of this APC isoform may contribute to the potential of RPE to migrate and proliferate.

Surgical treatment of extensive peripapillary choroidal neovascularization in elderly patients.

PURPOSE: To report the visual outcomes and complications of surgical removal of extensive peripapillary choroidal neovascularization (PPCNV) in elderly patients. DESIGN: Retrospective review. PARTICIPANTS: Seventeen consecutive eyes of 17 patients older than age 55 undergoing PPCNV resection. METHODS: Retrospective review of eyes undergoing surgical removal of extensive PPCNV via pars plana vitrectomy. MAIN OUTCOME MEASURES: Preoperative and postoperative Snellen visual acuity. RESULTS: The mean age of patients was 76.9 years, and the mean duration of follow-up was 29.8 months. In 6 of 17 eyes, the PPCNV was extrafoveal; in two eyes, it was juxtafoveal; and in nine eyes, it was subfoveal. The cause of CNV was idiopathic (nine eyes), age-related macular degeneration (six eyes), presumed ocular histoplasmosis syndrome (one eye), and inflammation (one eye). All eyes were ineligible for laser treatment by MPS criteria. In eyes with extrafoveal CNV, the preoperative Snellen visual acuity ranged from 20/25 to 20/300, and the final visual acuity ranged from 20/40 to 20/800. The two eyes with juxtafoveal CNV had preoperative visual acuities of 20/125 and 20/300, and both had a postoperative acuity of 20/200. Eyes with subfoveal CNV had a range of preoperative visual acuity from 20/125 to 20/800, whereas the final visual acuity ranged from 20/30 to hand motions. Four of the nine eyes with subfoveal lesions had improved visual acuity. Overall, the final visual acuity was stable or improved in six eyes and worsened in 11 eyes. CNV recurrence was noted in four eyes and required reexcision, laser photocoagulation, or both. Surgical complications included retinal detachment (two eyes), retinal hole and epiretinal membrane (one eye), cystoid macular edema (two eyes), and subsequent cataract extraction (four eyes). CONCLUSIONS: Surgical removal of extensive PPCNV in the elderly does not often yield improvement or stabilization of visual acuity. However, 6 of 17 patients had stable or improved visual acuity.