SMALL-GAUGE TECHNIQUES FOR REMOVING A FLUOCINOLONE ACETONIDE IMPLANT.

PURPOSE: Long-acting injectable fluocinolone releasing implants are used in clinical practice. Although limited in scope, situations may arise where removal of the implant is warranted. We set out to describe possible explantation techniques and to determine whether these implants can be safely removed from a standard sclerotomy or eliminated using a vitrectomy system. METHODS: A vitreoretinal surgery system was designed using a porcine eye model. A fluocinolone implant was injected into the vitreous cavity. Pars plana vitrectomy was performed and the vitreous cavity was infused with balanced salt solution. The injected implants were removed from 23-Gauge (G) and 25-Gauge (G) vitrectomy cannulas with 27-G forceps. The implants were examined under the microscope for induced defects. Implants were injected into the eye model and eliminated using a 23-G and 25-G vitrector system. RESULTS: The implant was removed from both the 23-G and 25-G vitrectomy cannulas with only mild structural damage to the implant. During implant extraction through the 25-G sclerotomy, the cannula was dislodged from the incision along with the implant. The most technically challenging portion involved aligning the implant coaxially to allow for removal en bloc through the sclerotomy site. Implants could be eliminated using both the 23-G and 25-G vitrector using a low-cut rate. CONCLUSION: The fluocinolone implant was removed safely via standard 23-G or 25-G vitrectomy systems. It is unknown whether intraocular manipulation will affect pharmacokinetics of drug delivery if the implant is not explanted.

Haptic Erosion Following Sutureless Scleral-fixated Intraocular Lens Placement.

PURPOSE: To describe the clinical features and visual outcomes of eyes with conjunctival haptic erosion after sutureless intrascleral (SIS) fixated intraocular lens (IOL) placement. DESIGN: Retrospective case series. SUBJECTS: Patients experiencing haptic erosion after SIS fixation between January 1, 2013, and March 1, 2022. METHODS: A multicenter, multisurgeon, retrospective review. MAIN OUTCOME MEASURES: Clinical features, visual outcomes, and treatment options following haptic erosions after SIS fixation. RESULTS: Nineteen eyes with haptic erosion were identified. The mean age at initial SIS fixation was 64 ± 12 years (range, 38-81 years). There were 5 (26%) eyes with a history of conjunctiva involving ocular surgery, including scleral buckle surgery and tube shunt surgery. Trocar-assisted fixation was performed in 15 (79%) eyes, whereas needle fixation was used in 4 (21%) eyes. Eighteen (95%) sets of haptics were flanged with a low temperature cautery. Seventeen (90%) sets of haptics were externalized superiorly and inferiorly, and 2 (10%) sets of haptics were externalized nasally and temporally. Haptics were covered by conjunctiva in 14 (74%) eyes and by scleral flap in 5 (26%) eyes. All patients experienced a single haptic erosion, of which 8 (43%) were located superiorly, 9 (47%) inferiorly, and 2 (10%) temporally. The mean interval between the initial SIS fixation and haptic erosion was 278 ± 437 days. After correction of the erosion, 18 (95%) eyes had a stable IOL at the last follow-up, with no recurrence of haptic erosion. In this series, there were no cases of endophthalmitis. CONCLUSIONS: Haptic erosion is a notable complication after SIS fixated IOL surgery but may be repaired with favorable visual outcomes. Careful evaluation of the conjunctiva should be considered before the surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Impact of Coronavirus Disease 2019 Restrictions on Retinal Detachment: A Multicenter Experience.

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

Intraocular pressure (IOP) after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations-GEODEX-IOP study.

PURPOSE: To analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations. METHODS: The medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%). RESULTS: Amongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group. CONCLUSION: Latino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

Effects of Brimonidine on Retinal Pigment Epithelial Cells and Müller Cells Exposed to Amyloid-Beta 1-42 Peptide In Vitro.

BACKGROUND AND OBJECTIVE: To evaluate whether brimonidine can prevent cytotoxicity in human retinal pigment epithelial (RPE) and Müller (MIO) cells after exposure to amyloid-beta 1-42 (Aß42). MATERIALS AND METHODS: An in vitro model of geographic atrophy (GA), which is an end-stage complication of age-related macular degeneration (AMD), simulated with the application of Aß42 in cell culture. RPE and MIO cells were pretreated with brimonidine for 6 hours, then exposed to 10µM Aß42 for 24 hours. Several concentrations (one time [1×], two times [2×], and five times [5×]) of brimonidine were used to assess for a dose-related effect. Assays were immediately run following the treatment period. 2',7'-Dichlorofluorescein diacetate was used to assess reactive oxygen species production, the MTT assay was used to assess cell viability, and the JC-1 dye assay was used to assess mitochondrial membrane potential. The main outcome measures were reactive oxygen species (ROS) production, cell viability, and mitochondrial membrane potential (ΔΨm) of RPE and MIO cells following the treatment phase. RESULTS: High-dose (5×) brimonidine was capable of reducing ROS production in RPE and MIO cells with exposure to Aß42. The application of Aß42 alone did not trigger a rise in ROS production. Brimonidine was unable to rescue cell viability and ΔΨm after exposure to Aß42 in both cell cultures. Instead, high-dose (5×) brimonidine appeared to increase the toxicity to cell viability and ΔΨm in cultures exposed to Aß42. However, this was not due to medication toxicity alone, because high-dose (5×) brimonidine without exposure to Aß42 did not affect the cell viability in both cell types. CONCLUSION: Brimonidine may have a role in preventing oxidative cellular injury in AMD. However, this role does not appear to translate into protection against some of the cytotoxic effects observed from this in vitro model of GA. In this cellular model of GA, brimonidine is able to reduce oxidative stress but is unable to rescue cell viability or prevent mitochondrial dysfunction. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S23-S28.].

Age-Stratified Analysis of Diabetes and Pseudophakia Effects on Corneal Endothelial Cell Density: A Retrospective Eye Bank Study.

PURPOSE: To perform an age-stratified analysis of the effect of diabetes and pseudophakia on corneal endothelial cell density (ECD). METHODS: This is a comparative analysis of donor characteristics from data supplied by the Lions Eye Institute for Transplant and Research on tissue harvested from July 1, 2007, through May 23, 2014. The mixed-effects model was used to compare age-adjusted mean corneal ECD between donors with and without diabetes. RESULTS: A total of 20,026 nondiabetic donor eyes and 13,617 diabetic donor eyes were included in this study. ECD was 2604 cells per square millimeter in nondiabetic corneas and 2576 cells per square millimeter in diabetic corneas (P < 0.001). Among phakic patients, diabetic ECD was significantly less in the middle-age subgroups: -33 cells per square millimeter in the 21-to-40-year-old subgroup (P = 0.048) and -25 cells per square millimeter in the 41-to-60-year-old subgroup (P = 0.009). Among pseudophakic patients, diabetic ECD was significantly less only in the subgroup 61 years or older: -56 cells per square millimeter (P = 0.026). The magnitude of difference in ECD between phakic and pseudophakic donors was greater in patients with diabetes in the subgroup 61 years or older (P < 0.001). CONCLUSIONS: Donor eyes with a history of diabetes had a slightly lower ECD (-29 cells/mm) than eyes without a history of diabetes. Although this statistical relationship is consistent with our pathophysiologic understanding of diabetes and the corneal endothelium, such a minor difference in ECD would be expected to have minimal clinical impact on overall corneal endothelial function.

Iris mattress suture: a technique for sectoral iris defect repair.

Achieving a cosmetic and functional outcome from iris defect repair is a surgical challenge. We describe an adaptation of techniques to address a case of 2.5 clock hours of sectoral iris tissue defect. Our method combines Siepser's modified closed-chamber sliding knot technique with the placement of a double-armed iris mattress suture to approximate iris tissue to the scleral wall and thereby create a pseudo-iris root. This technique reduces glare and achieves a cosmetic outcome for the patient.

Do statins have a role in the prevention of age-related macular degeneration?

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide for which preventative therapies are few. Evidence suggesting shared common risk factors and mirrored pathophysiology between cardiovascular disease and AMD led to the hypothesis that hydroxymethylglutaryl-CoA reductase inhibitors (statins) could be helpful in preventing AMD. For over a decade, observational studies have repeatedly investigated this hypothesis with conflicting conclusions. Although many reports conclude that statin use has no effect on the risk of AMD, no randomized controlled trial has yet been completed. Furthermore, relatively few studies factor characteristics of statin use into their analysis. A few studies have observed an incompletely explained protective effect against drusen, a funduscopic finding associated with AMD. Although there is insufficient evidence for a preventive effect of statins on dry AMD, there does seem to be stronger evidence against any effect on the development of exudative AMD. Overall, we find that there is insufficient evidence to conclude whether statin use is helpful in preventing AMD.

Gene expression profile identifies tyrosine kinase c-Met as a targetable mediator of antiangiogenic therapy resistance.

PURPOSE: To identify mediators of glioblastoma antiangiogenic therapy resistance and target these mediators in xenografts. EXPERIMENTAL DESIGN: We conducted microarray analysis comparing bevacizumab-resistant glioblastomas (BRG) with pretreatment tumors from the same patients. We established novel xenograft models of antiangiogenic therapy resistance to target candidate resistance mediator(s). RESULTS: BRG microarray analysis revealed upregulation versus pretreatment of receptor tyrosine kinase c-Met, which underwent further investigation because of its prior biologic plausibility as a bevacizumab resistance mediator. BRGs exhibited increased hypoxia versus pretreatment in a manner correlating with their c-Met upregulation, increased c-Met phosphorylation, and increased phosphorylation of c-Met-activated focal adhesion kinase and STAT3. We developed 2 novel xenograft models of antiangiogenic therapy resistance. In the first model, serial bevacizumab treatment of an initially responsive xenograft generated a xenograft with acquired bevacizumab resistance, which exhibited upregulated c-Met expression versus pretreatment. In the second model, a BRG-derived xenograft maintained refractoriness to the MRI tumor vasculature alterations and survival-promoting effects of bevacizumab. Growth of this BRG-derived xenograft was inhibited by a c-Met inhibitor. Transducing these xenograft cells with c-Met short hairpin RNA inhibited their invasion and survival in hypoxia, disrupted their mesenchymal morphology, and converted them from bevacizumab-resistant to bevacizumab-responsive. Engineering bevacizumab-responsive cells to express constitutively active c-Met caused these cells to form bevacizumab-resistant xenografts. CONCLUSION: These findings support the role of c-Met in survival in hypoxia and invasion, features associated with antiangiogenic therapy resistance, and growth and therapeutic resistance of xenografts resistant to antiangiogenic therapy. Therapeutically targeting c-Met could prevent or overcome antiangiogenic therapy resistance.

Microarray analysis verifies two distinct phenotypes of glioblastomas resistant to antiangiogenic therapy.

PURPOSE: To identify mechanisms and mediators of resistance to antiangiogenic therapy in human glioblastoma. EXPERIMENTAL DESIGN: We carried out microarray gene expression analysis and immunohistochemistry comparing 21 recurrent glioblastomas progressing during antiangiogenic treatment with VEGF neutralizing antibody bevacizumab to paired pretreatment tumors from the same patients. RESULTS: Microarray analysis revealed that bevacizumab-resistant glioblastomas (BRG) had two clustering patterns defining subtypes that reflect radiographic growth patterns. Enhancing BRGs (EBRG) exhibited MRI enhancement, a long-established criterion for glioblastoma progression, and expressed mitogen-activated protein kinases, neural cell adhesion molecule-1 (NCAM-1), and aquaporin 4. Compared with their paired pretreatment tumors, EBRGs had unchanged vascularity and hypoxia, with increased proliferation. Nonenhancing BRGs (NBRG) exhibited minimal MRI enhancement but had FLAIR-bright expansion, a newer criterion for glioblastoma recurrence since the advent of antiangiogenic therapy, and expressed integrin α5, laminin, fibronectin1, and PDGFRß. NBRGs had less vascularity, more hypoxia, and unchanged proliferation than their paired pretreatment tumors. Primary NBRG cells exhibited more stellate morphology with a 3-fold increased shape factor and were nearly 4-fold more invasive in Matrigel chambers than primary cells from EBRGs or bevacizumab-naive glioblastomas (P < 0.05). CONCLUSION: Using microarray analysis, we found two resistance patterns during antiangiogenic therapy with distinct molecular profiles and radiographic growth patterns. These studies provide valuable biologic insight into the resistance that has limited antiangiogenic therapy to date.

CD133+ neural stem cells in the ependyma of mammalian postnatal forebrain.

The postnatal forebrain subventricular zone (SVZ) harbors stem cells that give rise to olfactory bulb interneurons throughout life. The identity of stem cells in the adult SVZ has been extensively debated. Although, ependymal cells were once suggested to have stem cell characteristics, subsequent studies have challenged the initial report and postulated that subependymal GFAP(+) cells were the stem cells. Here, we report that, in the adult mouse forebrain, immunoreactivity for a neural stem cell marker, prominin-1/CD133, is exclusively localized to the ependyma, although not all ependymal cells are CD133(+). Using transplantation and genetic lineage tracing approaches, we demonstrate that CD133(+) ependymal cells continuously produce new neurons destined to olfactory bulb. Collectively, our data indicate that, compared with GFAP expressing adult neural stem cells, CD133(+) ependymal cells represent an additional-perhaps more quiescent-stem cell population in the mammalian forebrain.