Heterogeneity in disease activity, frequency of treatments, and visual outcomes among patients with retinal vein occlusion: relationship between injection need and vision with as-needed ranibizumab.

BACKGROUND/AIMS: We characterised the relationships between monitoring frequency, ranibizumab injection need and vision in patients receiving as-needed (pro re nata; PRN) ranibizumab for macular oedema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in this post-hoc analysis of SHORE and HORIZON. METHODS: Patients aged 18 years and older with macular oedema due to BRVO/CRVO were included in this analysis. Injection frequency and best-corrected visual acuity (BCVA) were evaluated by PRN injection frequency in the PRN dosing phase (months (M) 7-15) of SHORE and through 12 months of HORIZON. Prespecified PRN re-treatment criteria for each trial were based on protocol-prespecified BCVA and optical coherence tomography outcomes. RESULTS: After the initial 7 monthly ranibizumab injections, patients in SHORE gained a mean of 18.3 letters from baseline. Patients randomised to PRN, on average, maintained these gains. However, some patients experienced additional mean gains, whereas others suffered losses (range 4.0 (95% CI 0.7 to 7.3) to -4.6 (95% CI -11.8 to 2.6) letters in patients who received 0 and 6-7 PRN injections, respectively). In BRAVO and CRUISE (lead-in trials), patients experienced mean gains from baseline to M6 (monthly dosing) of 19.3 and 15.0 letters, respectively, with gains maintained with PRN from M6 to M12. However, mean BCVA changes from baseline to M12 varied in HORIZON (range -0.4 (95% CI -2.5 to 1.6) to -3.6 (95% CI -6.2 to -1.0) letters in patients who received zero and six injections, respectively, during the preceding PRN phase of BRAVO and CRUISE). CONCLUSION: The BRVO/CRVO population is heterogenous with a varied response to ranibizumab treatment.

Safety and tolerability of intravitreal umedaptanib pegol (anti-FGF2) for neovascular age-related macular degeneration (nAMD): a phase 1, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of a single-dose intravitreal umedaptanib pegol (anti-FGF2, investigational new drug) for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: Nine participants who had a diagnosis of refractory nAMD were enrolled and received a single intravitreal injection of umedaptanib pegol at increasing doses of 0.2, 1.0 or 2.0 mg in the study eye. RESULTS: All three doses of umedaptanib pegol evaluated in the study were safe and well tolerated. No severe adverse event (AE) was observed in the study. There was an improvement in retinal fluid measured by central subfield thickness (CST) in most subjects. Remarkably, all three subjects who received 2.0 mg/eye showed improvement of more than 150 µm. CONCLUSIONS: Intravitreal umedaptanib pegol was safe, well tolerated, and demonstrated an indication of bioactivity in participants that have persistent subretinal fluid refractory to the treatment with anti-VEGFs.

Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients.

BACKGROUND/OBJECTIVE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD. METHODS: Three phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five naïve nAMD patients who had not received any prior anti-VEGF treatment. RESULTS: The TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, naïve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients. CONCLUSIONS: These results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.

Injectable Devices for Delivery of Liquid or Solid Protein Formulations.

Sustained delivery of protein therapeutics remains a largely unsolved problem across anatomic locations. Miniaturized devices that can provide sustained delivery of protein formulations have the potential to address this challenge via minimally invasive administration. In particular, methodologies that can optimize protein formulation independent of device manufacture have the greatest potential to provide a platform suitable for wide applications. The techniques developed here demonstrate the fabrication of tubular devices for sustained release of protein therapeutics. Utilizing a dip-casting process, fine-scale tubes can be reliably produced with wall thickness down to 30 µm. Techniques were developed that enabled effective loading of either solid or liquid formulations, while maintaining a cylindrical form-factor compatible with placement in a 22-gauge needle. Further, highly compacted protein pellets that approach the expected density of the raw materials were produced with a diameter (∼300 µm) suitable for miniaturized devices. Release from a solid-loaded device was capable of sustaining release of a model protein in excess of 400 days. Given significant interest in ocular applications, intravitreal injection was demonstrated in a rabbit model with these devices. In addition, to simulate repeated injections in ocular applications, serial intravitreal injection of two devices in a rabbit model demonstrated acceptable ocular safety without significant intraocular inflammation from clinical exam and histology.

Macular Atrophy Incidence, Progression, and Visual Acuity Effects in 5-Year Treatment of Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Macular atrophy (MA) contributes to declining vision during prolonged anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) so greater understanding of its incidence, evolution, and impact on visual acuity is merited. MATERIALS AND METHODS: This is a retrospective review of nAMD patients receiving anti-VEGF therapy for ≥ 5 years. Near-infrared reflectance images and vision data were extracted every 6 months. MA lesion areas were measured using ImageJ. RESULTS: Vision showed a mean decline of -1.2 letters/year. Eyes with MA showed a greater decrease of -1.6 letters/year compared to eyes without MA (-0.7 letters/year). Cumulative incidence of MA was 38% at 5 years. MA was significantly associated with declining vision, showing a -0.7 letter decrease for every 1 mm2 increase in lesion size. CONCLUSION: Over a 5-year course of nAMD treatment, MA affected most eyes, and MA progression was significantly associated with vision decline. [Ophthalmic Surg Lasers Imaging Retina 2022;53:546-552.].

BILATERAL ENTEROCOCCUS FAECALIS ENDOPHTHALMITIS WITH MULTIPLE RECURRENCES.

PURPOSE: To describe the first case report of a bilateral recurrent Enterococcus faecalis endophthalmitis postcataract surgery. METHODS: Case report with a description of the timeline, diagnosis, and management of a patient with bilateral recurrent E. faecalis endophthalmitis. RESULTS: An 89-year-old man presented 6 weeks' postcataract surgery with pain, tearing, and blurred vision in the left eye. B-scan ultrasonography revealed vitritis and cultures postvitrectomy grew E. faecalis. There was gradual improvement in vision postintravitreal vancomycin administration. Four years later, the patient experienced another episode of E. faecalis endophthalmitis in the right eye postcataract extraction, followed by several additional episodes in both eyes posttreatment. CONCLUSION: Enterococcus faecalis is a rare but highly virulent cause of endophthalmitis that may remain sequestered in the capsular bag, despite aggressive treatment. Even after recurrent episodes, early vitrectomy and aggressive antibiotic therapy may prove to be effective in preventing vision loss.

Rhegmatogenous retinal detachment masquerading as exudative panuveitis with intense anterior chamber inflammatory reaction.

PURPOSE: This is a retrospective case report illustrating the diagnostic and therapeutic challenges associated with a chronic rhegmatogenous retinal detachment masquerading as a severe panuveitis with intense anterior chamber inflammation. We have included clinical features, anterior segment and fundus photography, B-scan ultrasonography, fluorescein angiography, and intraoperative findings. OBSERVATIONS: A 26-year-old male presented with features of unilateral panuveitis: hypotony, anterior segment inflammation (posterior synechiae and anterior chamber cell with fibrin clumping), diffuse choroidal thickening, and retinal detachment. Laboratory investigations for infectious or rheumatologic processes were negative, and empiric systemic corticosteroid therapy was unsuccessful. This prompted suspicion for an alternate primary etiology, and pars plana vitrectomy revealed small retinal breaks as the underlying cause of the retinal detachment and inflammation. CONCLUSIONS: Rhegmatogenous retinal detachments are a known cause of intraocular inflammation. Nevertheless, it remains a challenge to recognize retinal breaks in this setting, particularly with robust anterior segment inflammation and posterior findings resembling severe exudative uveitis. Being aware of this unique presentation may prevent delays in diagnosis and have important prognostic implications.

Glass intraocular foreign body removal with a nitinol stone basket.

PURPOSE: Glass intraocular foreign bodies (IOFBs) complicate up to 14% of all IOFB cases and require specialized instruments for removal. We present a case of ocular trauma with two large glass IOFBs removed using a nitinol stone basket (NSB) designed for kidney stone extraction in the ureter and calyces. OBSERVATIONS: An adult male suffered a restrained motor vehicle accident. Radiographic computed tomography identified a 9-mm polygonal IOFB within the posterior segment of the right eye. A staged procedure was performed with repair of the ruptured globe followed by 23-gauge pars plana vitrectomy, pars plana lensectomy, and removal of the IOFBs using a NSB. CONCLUSION: At post-operative month one, visual acuity was correctable to 20/60. The retina remained attached and the patient was recovering without complication. IMPORTANCE: Large glass IOFBs are poorly gripped by standard ophthalmic forceps due to their smooth surface, large size, and irregular shape. The NSB is an effective instrument for controlled removal of glass IOFBs. Further customized design may adapt this device for additional intraocular procedures.

Anti-Angiogenic and Anti-Scarring Dual Action of an Anti-Fibroblast Growth Factor 2 Aptamer in Animal Models of Retinal Disease.

Currently approved therapies for age-related macular degeneration (AMD) are inhibitors against vascular endothelial growth factor (VEGF), which is a major contributor to the pathogenesis of neovascular AMD (nAMD). Intravitreal injections of anti-VEGF drugs have shown dramatic visual benefits for AMD patients. However, a significant portion of AMD patients exhibit an incomplete response to therapy and, over the extended management course, can lose vision, with the formation of submacular fibrosis as one risk factor. We investigated a novel target for AMD treatments, fibroblast growth factor 2 (FGF2), which has been implicated in the pathophysiology of both angiogenesis and fibrosis in a variety of tissue and organ systems. The anti-FGF2 aptamer, RBM-007, was examined for treatment of nAMD in animal models. In in vivo studies conducted in mice and rats, RBM-007 was able to inhibit FGF2-induced angiogenesis, laser-induced choroidal neovascularization (CNV), and CNV with fibrosis. Pharmacokinetic studies of RBM-007 in the rabbit vitreous revealed high and relatively long-lasting profiles that are superior to other approved anti-VEGF drugs. The anti-angiogenic and anti-scarring dual action of RBM-007 holds promise as an additive or alternative therapy to anti-VEGF treatments for nAMD.

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

PURPOSE: We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo. METHODS: Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 µm for timolol and brimonidine compartments, respectively. In vitro release kinetics were measured in pH- and temperature-controlled fluid chambers. Empty or drug-loaded devices were implanted intracamerally in normotensive rabbits for up to 13 weeks with weekly measurements of IOP. For ocular concentrations, rabbits were euthanized at 4, 8, or 13 weeks, aqueous fluid was collected, and ocular tissues were dissected. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. RESULTS: In vitro studies show zero-order release kinetics for both timolol (1.75 µg/day) and brimonidine (0.48 µg/day) for up to 60 days. In rabbit eyes, the device achieved an average aqueous fluid concentration of 98.1 ± 68.3 ng/mL for timolol and 5.5 ± 3.6 ng/mL for brimonidine. Over 13 weeks, the drug-loaded co-delivery device resulted in a statistically significant cumulative reduction in IOP compared to untreated eyes (P < 0.05) and empty-device eyes (P < 0.05). CONCLUSIONS: The co-delivery device demonstrated a zero-order release profile in vitro for 2 hypotensive agents over 60 days. In vivo, the device led to significant cumulative IOP reduction of 3.4 ± 1.6 mmHg over 13 weeks. Acceptable ocular tolerance was seen, and systemic drug levels were unmeasurable.

Device design methodology and formulation of a protein therapeutic for sustained release intraocular delivery.

Despite years of effort, sustained delivery of protein therapeutics remains an unmet need due to three primary challenges - dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir-based thin film devices suitable for long-acting protein delivery to the back of the eye. First, the challenge of formulating highly concentrated protein in a device reservoir was addressed by improving stability with solubility-reducing excipients. Next, predictive correlations between design parameters and device performance were developed to provide a methodology to achieve a target product profile. Prototype devices were designed using this methodology to achieve desired device size, release rate, therapeutic payload, and protein stability, assessed by in vitro studies. Finally, prototype tolerability was established in a non-human primate model. The design methodology presented here is widely applicable to reservoir-based sustained delivery devices for proteins and provides a general device design framework.

Long-term intraocular pressure reduction with intracameral polycaprolactone glaucoma devices that deliver a novel anti-glaucoma agent.

Long-term treatment of glaucoma, a major leading cause of blindness, is challenging due to poor patient compliance. Therefore, a drug delivery device that can achieve drug release over several months can be highly beneficial for glaucoma management. Here, we evaluate the long-term pharmacokinetics and therapeutic efficacy of polycaprolactone intracameral drug delivery devices in rabbit eyes. Our study showed that a single drug delivery device loaded with a proprietary hypotensive agent, DE-117, reduced intraocular pressure in normotensive rabbits significantly for 23weeks. In addition, we demonstrated that concentration of DE-117 and its hydrolyzed active form (hDE-117) was maintained in the aqueous humor and the target tissue (iris-ciliary body) up to 24weeks. Our proof-of-concept glaucoma implant shows potential as a long-term treatment that circumvents patient compliance barriers compared to current treatment via eye drops.

Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic Calcifications Using a Nitinol Loop: A Case Series.

Deposition of dystrophic calcifications on the posterior surface of silicone intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis. Accumulation of silicone oil droplets on the posterior surface of silicone IOLs in silicone-filled eyes has also been reported. Recently, a novel technique to manually remove dystrophic calcifications using a nickel titanium loop (Finesse Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL exchange. Here, the authors report their outcomes with this technique in five eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].

Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma.

PURPOSE: We developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months. METHODS: The release rates of DE-117-loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE-117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS). RESULTS: In vitro release of DE-117 showed zero-order release with a release rate of 0.5 µg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE-117 and hDE-117 (the hydrolyzed active form of DE-117) in ocular tissues (cornea, iris-ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE-117 and its conversion to hDE-117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE-117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device. CONCLUSIONS: Proof-of-concept PCL drug delivery devices containing DE-117 show promise as a long-term glaucoma treatment based on their zero-order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues.

In vivo and in vitro sustained release of ranibizumab from a nanoporous thin-film device.

Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and retina carries ocular risks, a high patient treatment burden, and compliance barriers that can lead to suboptimal treatment. Here we introduce a device that produces sustained release of ranibizumab in the vitreous cavity over the course of several months. Composed of twin nanoporous polymer thin films surrounding a ranibizumab reservoir, these devices provide release of ranibizumab over 16 weeks in vitro and 12 weeks in vivo, without exhausting the initial drug payload. Following implantation in vivo, devices were well-tolerated and showed no sign of immune response. This platform presents a potential solution to the challenge of delivering protein therapeutics to the vitreous and retina for sustained periods of time.

Predictors of Macular Atrophy Detected by Fundus Autofluorescence in Patients With Neovascular Age-Related Macular Degeneration After Long-Term Ranibizumab Treatment.

BACKGROUND AND OBJECTIVE: To study the relationship between baseline morphologic characteristics of the choroidal neovascular (CNV) lesion and long-term development of macular atrophy in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA). PATIENTS AND METHODS: Certified graders evaluated baseline and 7-year follow-up (SEVEN-UP study) images of 41 eyes from the MARINA/ANCHOR and HORIZON trials. Using GRADOR software and stepwise linear regression, graders correlated lesion characteristics on fluorescein angiography (FA) at both visits with areas of definite decreased autofluorescence (DDAF) on fundus autofluorescence (FAF) imaging at the SEVEN-UP visit. RESULTS: Three of 41 eyes (7.3%) had macular atrophy on FA at baseline (mean ± standard deviation [SD] size: 0.29 mm(2) ± 1.50 mm(2)), 29 (70.7%) at SEVEN-UP (mean ± standard deviation [SD] area: 7.42 mm(2) ± 7.97 mm(2)). On FAF imaging at the SEVEN-UP visit, all 41 eyes (100%) had DDAF (mean ± SD size: 10.29 mm(2) ± 8.07 mm(2)). Variables significantly associated with area of DDAF at the SEVEN-UP visit were the area of leaking CNV lesion components (coefficient: 0.953; P < .001), the area of other lesion components (coefficient: 1.094; P = .038), and the area of retinal pigment epithelial (RPE) atrophy (coefficient: 1.334; P = .040) on baseline FA imaging. CONCLUSION: The area of DDAF at more than 7 years after initiation of ranibizumab therapy was 35% larger than the original CNV lesion. The baseline area of leaking CNV and other components of the CNV lesion and the baseline area of RPE atrophy were important predictors of the area of definite decreased autofluorescence, presumably corresponding to areas of photoreceptor and RPE loss. The findings from this study may guide hypothesis generation for future AMD trials.

Fellow Eye Comparisons for 7-Year Outcomes in Ranibizumab-Treated AMD Subjects from ANCHOR, MARINA, and HORIZON (SEVEN-UP Study).

PURPOSE: To compare study and fellow eyes in subjects with age-related macular degeneration (AMD) for 7-year outcomes arising from contrasting treatment histories and disease statuses. DESIGN: Multicenter cohort study, predetermined secondary analysis. PARTICIPANTS: A total of 65 participants from the ranibizumab-treatment arms of the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR), Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the Treatment of Neovascular AMD (MARINA), and Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON) trials, recruited for an update evaluation from 14 study sites. METHODS: Seven-year visual outcomes and retinal imaging data were compared with the ANCHOR, MARINA, and HORIZON databases. Under the ANCHOR and MARINA protocols, study eyes had received monthly ranibizumab injections for the initial 2 years, during which fellow eyes were prohibited from anti-vascular endothelial growth factor (VEGF) treatments. MAIN OUTCOME MEASURES: Percentage of subjects with study eye vision better than fellow eye, vision change from baseline to year 7, and mean area of macular atrophy (MA) were predetermined secondary end points. RESULTS: Fellow eyes with exudative AMD had received a mean 7.3 total injections of anti-VEGF agents in the mean 3.4 years off-study. For the 35% of subjects with exudative AMD in both eyes at baseline, within-patient comparisons at year 7 showed better vision in the study eye in 82%, with better mean final vision in study eyes (54.7 vs. 27.3 letters in fellow eyes, P < 0.001). Also in this subgroup, study eyes, which had received 2 years of high-frequency ranibizumab, had less severe MA than the respective fellow eye at year 7 in 88% of patients (mean area ± standard deviation 2.8±2.2 mm(2) vs. 5.8±2.5 mm(2) in the fellow eyes, P = 0.0013). Final fellow eye vision outcome was significantly correlated with MA severity (coefficient -6.95, P < 0.001), and patients' inter-eye vision difference corresponded to the degree of MA asymmetry. CONCLUSIONS: Exudative fellow eyes remained at risk for further vision decline in later years under management with low-frequency anti-VEGF therapy. In patients with bilateral exudative AMD at baseline, final vision at year 7 was significantly better in study eyes than in fellow eyes, and MA was less severe. Macular atrophy area correlated with final visual outcomes, determined inter-eye vision differences, and was not attributable to high-frequency ranibizumab therapy.

Same-Day Versus Next-Day Repair of Fovea-Threatening Primary Rhegmatogenous Retinal Detachments.

PURPOSE: To evaluate the outcomes of same-day versus next-day repair of fovea-threatening rhegmatogenous retinal detachments (FT RRD). DESIGN: Retrospective, multi-surgeon observational case series. METHODS: Operative reports and medical records were reviewed to evaluate a number of visual and anatomic outcomes, including presenting features, intraoperative complications, and postoperative results in the repair of primary FT RRD undergoing same-day versus next-day repair with scleral buckling, pars plana vitrectomy, or both procedures. PARTICIPANTS: A total of 96 consecutive patients (43 same-day, 45 next-day, and eight two days later) were compared. RESULTS: There was no statistically significant difference in visual outcomes between same-day and next-day repair at postoperative months 3 and 6 and at last follow-up (month 3 mean BCVA 20/30 same day; 20/32 next day; p = 0.82). Preoperative vision was strongly correlated with postoperative acuity. Effect of differences in length or type of visual symptoms, location of RRD, gender, or lens status on postoperative month 3 best-corrected visual acuity (BCVA) was not statistically significant. Overall, 85% of patients had a BCVA of 20/40 or better at postoperative month 3. Reoperation rate and intraoperative complications were not statistically different between the two groups. Re-attachment was achieved in all but one patient in both groups. Time in the operating room was longer for same-day surgery (2.98 ± 0.46 hours) compared to next-day surgery (2.54 ± 0.38 hours) (p < 0.001), which was statistically significant even when factoring in the type of surgery performed. However, one case did progress to a macula-off detachment in a superior RRD with breaks found in lattice degeneration. CONCLUSION: Next-day surgery provided equivalent visual outcomes. Emergent, same-day surgery has logistical and resource implications as it may be more expensive, may necessitate rescheduling of previously booked cases, and may limit preoperative examination by the surgeon and perioperative team.

In Vitro and In Vivo Sustained Zero-Order Delivery of Rapamycin (Sirolimus) From a Biodegradable Intraocular Device.

PURPOSE: We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. METHODS: Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. RESULTS: In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. CONCLUSIONS: Microporous PCL thin film devices demonstrate good ocular compatibility and the ability to release rapamycin locally to the eye over the course of many weeks.