Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease.

Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases. Design: Experimental study. Subjects: Brown Norway rats and New Zealand White Cross rabbits. Methods: Preclinical study data of RO-101 in terms of target-specific enzyme-linked immunosorbent assay binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser choroidal neovascular membrane animal model, human umbilical vein endothelial cell migration, and biocompatibility was obtained. Where applicable, study data were compared with other anti-VEGF agents. Main Outcome Measures: Binding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. Results: RO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable to or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. Conclusions: RO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates a strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The real-world efficacy and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study - 6 month results.

BACKGROUND/OBJECTIVE: Investigate real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). SUBJECTS/METHODS: Multicenter, retrospective chart review was conducted on patients treated with faricimab for nAMD from February 2022 to September 2022. Collected data includes background demographics, treatment history, best-corrected visual acuity (BCVA), anatomic changes, and adverse events as safety markers. The main outcome measures are changes in BCVA, changes in central subfield thickness (CST) and adverse events. Secondary outcome measures included treatment intervals and presence of retinal fluid. RESULTS: After one injection of faricimab, all eyes (n = 376), previously-treated (n = 337) and treatment-naïve (n = 39) eyes demonstrated a + 1.1 letter (p = 0.035), a + 0.7 letter (p = 0.196) and a + 4.9 letter (p = 0.076) improvement in BCVA, respectively, and a - 31.3 µM (p < 0.001), a - 25.3 µM (p < 0.001) and a - 84.5 µM (p < 0.001) reduction in CST, respectively. After three injections of faricimab, all eyes (n = 94), previously-treated (n = 81) and treatment-naïve (n = 13) eyes demonstrated a + 3.4 letter (p = 0.03), a + 2.7 letter (p = 0.045) and a + 8.1 letter (p = 0.437) improvement in BCVA, and a - 43.4 µM (p < 0.001), a - 38.1 µM (p < 0.001) and a - 80.1 µM (p < 0.204) reduction in CST, respectively. One case of intraocular inflammation was observed after four injections of faricimab and resolved with topical steroids. One case of infectious endophthalmitis was treated with intravitreal antibiotics and resolved. CONCLUSIONS: Faricimab has demonstrated improvement or maintenance of visual acuity for patients with nAMD, along with rapid improvement of anatomical parameters. It has been well-tolerated with low incidence of treatable intraocular inflammation. Future data will continue to investigate faricimab for real-world patients with nAMD.

Implementation and challenges unique to teleretinal diabetic retinal screening (TDRS) in a private practice setting in the United States.

PURPOSE: Adherence rates to published guidelines for diabetic retinopathy (DR) screening is between 35 and 60%. We evaluate a teleretinal DR screening (TDRS) program in a private practice vertically integrated system to increase compliance with retinal screening. METHODS: A retrospective pre-post intervention longitudinal study was conducted in a private endocrinology practice using TDRS as the primary intervention. Compliance rates for diabetic retinal screening were compared between December 31, 2016 and December 31, 2018. RESULTS: A total population of 3479 patients were evaluated. Retinal screening compliance improved from 56.5% of patients (1964) pre-intervention to 59.3% of patients (2064) post intervention. The McNemar test was used for statistical analysis and found the change significant (p = 0.004). CONCLUSIONS: TDRS as an adjunct tool in a private practice endocrinology office significantly improved screening rates and can increase access to recommended diabetic eye care. However, the improvement in screening rates was smaller than other types of practice settings. We explore some of the unique challenges to implementation of TDRS in private practice settings.

Development of a laser controlled device to modulate intraocular pressure.

INTRODUCTION: The current standard of treatment for glaucoma is trabeculectomy. The use of glaucoma drainage devices has increased in recent years since its efficacy and safety was established as it provides an alternative surgical option. A downfall of these devices is the lack of proper flow rate control. Areas covered: In this paper we describe a glaucoma drainage device regulator that has already been protoyped and undergone initial testing. It consists of an implantable device with a semipermeable membrane that is used during glaucoma surgery and can be opened with either thermal or photodisruptive laser to adjust the amount of flow precisely and non-invasively, addressing the current difficulties of glaucoma surgeries. A literature search was conducted using MEDLINE and manuscript references for studies published in English between 2000 and 2015 using the terms glaucoma, trabeculectomy and glaucoma drainage devices. Expert commentary: The GDDR device can decrease surgical risk and allow surgeons to post-operatively adjust flow as clinically needed using a non-invasive method. Further testing is planned to substantiate these initial results and evaluate the device's biocompatibility, tunability and efficacy.

A nanopore membrane regulator device for laser modulated flow after glaucoma surgery.

Glaucoma, the second most common cause of blindness in the world, is a multifactorial disease with several risk factors, of which intraocular pressure (IOP) is a primary contributing factor. Filtration surgery is one of the most effective means to significantly lower IOP compared to medical or laser treatments, and it is typically reserved for advanced disease. However, there are high rates of postoperative complications associated with the procedure, often from over- or under-filtration. To address these problems, the glaucoma drainage device regulator (GDDR) implant was developed to allow post-operative control of aqueous flow and IOP. The device, a tube with a nanopore membrane, is placed beneath the scleral flap. Postoperatively, the membrane surface can be ruptured with a laser to augment flow through the system. This feature allows adjustable control of aqueous flow and diminishes the risk of hypotony in the early postoperative period.

Retina evaluation with nonmydriatic ultrawide-field color imaging after cataract extraction surgeries in asymptomatic patients.

BACKGROUND AND OBJECTIVE: To evaluate the role of nonmydriatic ultrawide-field (UWF) color retinal imaging as a screening tool in the follow-up of asymptomatic patients after cataract extraction surgeries. PATIENTS AND METHODS: A retrospective, observational case series. A review of electronic medical records identified patients after cataract extraction followed with UWF retinal imaging (Optos 200Tx; Optos, Dunfermline, Scotland). Images were graded and reviewed by a retina specialist. Outcome measures included image quality, the detection of peripheral lesions, and association with perioperative risk factors. RESULTS: Seventy-six eyes of 58 consecutive patients were enrolled. A good visualization of the peripheral retina was accomplished in more than 90% of patients. Peripheral lesions were identified in 40 eyes (52.6%) with no surgery-related retinal breaks and/or detachments. Additional pathologies were found in 35 eyes (46.1%). CONCLUSION: Nonmydriatic UWF color retinal imaging was found to be a useful screening tool in the follow-up of asymptomatic patients after cataract extraction in this series.

Laser Activated Flow Regulator for Glaucoma Drainage Devices.

PURPOSE: To assess the capabilities of a new glaucoma drainage device regulator in controlling fluid flow as well as to demonstrate that this effect may be titratable by noninvasive means. METHODS: A rigid eye model with two main ports was used. On the first port, we placed a saline solution column. On the second, we placed a glaucoma shunt. We then measured the flow and flow rate through the system. After placing the regulator device on the tip of the tube, we measured again with the intact membrane and with the membrane open 50% and 100%. For the ex vivo testing we used a similar setting, using a cadaveric porcine eye, we measured again the flow and flow rate. However, this time we opened the membrane gradually using laser shots. A one-way analysis of variance and a Fisher's Least Significant Difference test were used for statistical significance. We also calculated the correlation between the numbers of laser shots applied and the main outcomes. RESULTS: The flow through the system with the glaucoma drainage device regulator (membrane intact and 50% open) was statistically lower than with the membrane open 100% and without device (P < 0.05). The flow was successfully controlled by the number of laser shots applied, and showed a positive correlation (+ 0.9). The flow rate was almost doubled every 10 shots and statistically lower than without device at all time (P < 0.05). CONCLUSIONS: The glaucoma drainage device regulator can be controlled noninvasively with laser, and allows titratable control of aqueous flow. TRANSLATIONAL RELEVANCE: Initial results and evidence from this experiment will justify the initiation of in vivo animal trials with the glaucoma drainage device regulator; which brings us closer to possible human trials and the chance to significantly improve the existing technology to treat glaucoma surgically.

Reversal of paracentral occlusive retinopathy in a case of sickle cell disease using exchange transfusion.

Paracentral occlusive retinopathy is an uncommon manifestation of sickle cell disease. If macular ischemia is not reversed, permanent vision loss can result. The authors report the successful use of exchange transfusion to treat unilateral paracentral occlusive retinopathy secondary to sickle cell disease in a 23-year-old man with hemoglobin SS disease. Initial presentation demonstrated arteriolar occlusion, perivenous hemorrhages, vessel tortuosity, and areas of retinal ischemia. Visual acuity was count fingers, and the patient noted a paracentral scotoma. Following transfusion, there was restoration of arteriolar flow as documented with fluorescein angiogram, and visual acuity returned to 20/20.

23-gauge vitrectomy for retained lens material.

A technique for removal of retained lens material is described with a three-port 23-gauge vitrectomy system. Removal of the core vitreous is first performed, followed by removal of the cortical vitreous. All vitreous adhesions to the lens are cleared. The cut rate is then decreased to 1,500 cuts per minute, and vacuum increased to 600 mm Hg. The cortical lens material is cleared first, and then the nuclear material is taken with the same vitrectomy probe using the light pipe to assist in crushing the nuclear fragments. With this technique, even large dense nuclear and cortical retained lens material can be removed from the vitreous chamber without the need for a fragmatome.

TOR complex 2 (TORC2) in Dictyostelium suppresses phagocytic nutrient capture independently of TORC1-mediated nutrient sensing.

The TOR protein kinase functions in two distinct complexes, TOR complex 1 (TORC1) and 2 (TORC2). TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization. In its ecological niche, Dictyostelium engulf bacteria and yeast for nutrient capture. Despite the essential role of TORC1 in control of cellular growth, we show that nutrient particle capture (phagocytosis) in Dictyostelium is independent of TORC1-mediated nutrient sensing and growth regulation. However, loss of Dictyostelium TORC2 components Rictor/Pia, SIN1/RIP3 and Lst8 promotes nutrient particle uptake; inactivation of TORC2 leads to increased efficiency and speed of phagocytosis. In contrast to phagocytosis, we show that macropinocytosis, an AKT-dependent process for cellular uptake of fluid phase nutrients, is not regulated by either of the TOR complexes. The integrated and balanced regulation of TORC1 and TORC2 might be crucial in Dictyostelium to coordinate growth and energy needs with other essential TOR-regulated processes.

Supra-tenon capsule placement of original Molteno vs Molteno 3 tube implants in black patients with refractory glaucoma: a single-surgeon experience.

OBJECTIVE: To evaluate the efficacy of supra-Tenon capsule placement of original Molteno vs Molteno 3 tube implants (Molteno Ophthalmic, Dunedin, New Zealand) in black patients with refractory glaucoma. METHODS: A retrospective study comparing the efficacy of supra-Tenon capsule placement of the original Molteno tube implant (130-mm(2) plate size) with the newer Molteno 3 tube implant (175-mm(2) plate size). Original Molteno tube implants were placed into 17 eyes and Molteno 3 tube implants into 27 eyes. RESULTS: Success was defined as an intraocular pressure of 18 mm Hg or less with or without adjuvant medical therapy. The median follow-up periods were 24 months (range, 12-48 months) for the original Molteno-implanted group (hereafter referred to as the original Molteno group) and 18 months (range, 12-48 months) for the Molteno 3-implanted group (hereafter referred to as the Molteno 3 group). The median preoperative intraocular pressures were 30 mm Hg for the original Molteno group and 24 mm Hg for the Molteno 3 group. The median postoperative intraocular pressures were 13 mm Hg for the original Molteno group and 14 mm Hg for the Molteno 3 group. Using Kaplan-Meier analysis, survival percentages were 71% for the original Molteno group and 88% for the Molteno 3 group. Log-rank test for comparison of survival indicated no significant difference between the 2 groups (P > .25). CONCLUSIONS: Supra-Tenon capsule placement of single-plate Molteno tube implants of different sizes can adequately control intraocular pressure in a group of patients with refractory glaucoma. Tenon capsule elimination seems to negate the effect of plate size.

Peters anomaly: review of the literature.

PURPOSE: Peters anomaly is a rare dramatic finding at birth and can be associated with other systemic malformations. We performed a literature review of multiple case reports and case series to better define the common characteristics and unusual findings associated with Peters anomaly. METHODS: A representative case is discussed followed by a literature review of multiple case reports and case series. The literature search was conducted for the years 1969 to 2009. Cases and case series were included in the review of published English ophthalmic literature. Cases were excluded if no information was reported on ocular and systemic malformations or if no information was reported on surgical interventions or outcomes. In addition, if cases did not report laterality of the lesion, they were excluded from the review. Fifty-eight cases were found that fit the above criteria, and the relevant cases were reviewed to better characterize the systemic malformations, interventions, and outcomes associated with Peters anomaly reported in the literature. RESULTS: Fifty-eight cases of Peters anomaly were reviewed. Of those cases reporting sex, 56% were men and 44% of cases were women. In terms of laterality, 67.2% of cases were bilateral versus 32.8% of cases that were unilateral. Moreover, bilateral cases of Peters anomaly were associated with a higher rate of systemic malformations (71.8%) versus unilateral Peters anomaly (36.8%). This difference was significant (P < 0.03 by Fischer exact test). In the 15 eyes where results of penetrating keratoplasty were reported, the overall success rate was 53%. However, the success rate was significantly higher in patients with Peters anomaly type I (87.5%), as opposed to those patients with Peters anomaly type II (14.2%) (P < 0.02 by Fischer exact test). DISCUSSION: The clinical features, epidemiology, genetics, complications, and treatments of Peters anomaly are presented. Cornea specialists who care for pediatric patients should be aware of the common and uncommon associations with Peters anomaly. Although bilateral Peters anomaly is much more commonly associated with systemic malformations, we believe that all patients with Peters anomaly should be screened for systemic malformations by both pediatricians and geneticists and undergo chromosomal analysis and molecular genetic testing.

Furuncular myiasis caused by Dermatobia hominis in a returning traveler.

Furuncular myiasis caused by Dermatobia hominis is endemic throughout Central and South America. We report a case of furuncular myiasis in a traveler returned from Costa Rica. The case is unique because the primary care physician obtained magnetic resonance images. The images, however, do not show any characteristic features that assist in diagnosis.