METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial.

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Reduction in Retinal Thickness Fluctuations After Treatment With Fluocinolone Acetonide Implant for DME: A Post-Hoc Analysis of the USER Study.

BACKGROUND AND OBJECTIVE: Assess fluocinolone acetonide implant (FAc) effects on diabetic macular edema (DME) retinal thickness fluctuations. PATIENTS AND METHODS: A post-hoc chart review of the real-world USER study analyzed patients receiving 0.2 µg/day FAc implant. The percentage of eyes with central subfield thickness (CST) of 300 µm or less were compared pre- and post-FAc implant; mean retinal thickness amplitude (RTA), retinal thickness standard deviation (RTSD), and two case studies were analyzed. RESULTS: One hundred thirty patients (mean age: 69.6 years) presented; CST was available for 120 of 160 treated eyes. Mean RTA decreased significantly post-FAc implant (P < .001) regardless of baseline visual acuity (VA). Correlations with last-observed VA (R2) were: RTA, 0.1197; retinal thickness standard deviation (RTSD), 0.1526; and area under the CST-time curve (AUC CST), 0.0981. After FAc implant, the percentage of eyes with CST of 300 µm or less was significantly greater versus baseline (P < .05). CONCLUSIONS: Retinal thickness fluctuations significantly declined after FAc and correlated with improvement in VA. Both RTSD and RTA measures correlated more closely to last observed VA than AUC CST itself. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:298-306.].

Central retinal artery occlusion on postoperative day one after vitreoretinal surgery.

PURPOSE: To report two cases of central retinal artery occlusion (CRAO) associated with vitreoretinal surgery. OBSERVATIONS: Two patients underwent vitreoretinal surgery and were diagnosed with CRAO on postoperative day one. Both had received retrobulbar anesthetic blocks, followed by pars plana vitrectomy in one patient and scleral buckling in the other patient. Best-corrected visual acuity at last follow-up was 20/40 and 20/400. CONCLUSIONS/IMPORTANCE: CRAO is a rare but serious adverse event after vitreoretinal surgery. The causative mechanism is not known in these patients.

Secondary Ocular Hypertension and the Risk of Glaucoma Surgery After Dexamethasone Intravitreal Implant in Routine Clinical Practice.

BACKGROUND AND OBJECTIVES: To determine the rate of ocular hypertension (OHT) after dexamethasone intravitreal implant in routine clinical practice and identify patient characteristics associated with a risk for glaucoma surgery. PATIENTS AND METHODS: The charts of 260 eyes from 221 patients with diabetic macular edema, retinal vein occlusion, uveitis, and macular edema secondary to various causes treated with one or more dexamethasone implants were reviewed. Intraocular pressure (IOP), medications, and glaucoma interventions were collected before and after implantation. RESULTS: The mean baseline IOP was 14.3 mm Hg ± 3.6 mm Hg, and after receiving dexamethasone implant(s), 26.2% and 7.7% of patients had IOP greater than 25 mm Hg and 35 mm Hg, respectively. There was evidence (P < .001) of an association between preexisting glaucoma or glaucoma suspect status (103 eyes) and need for glaucoma surgery, and 4.62% (12 eyes) required glaucoma surgery. CONCLUSIONS: Secondary OHT induced by the dexamethasone implant can usually be controlled by medications, but the incidence of OHT requiring glaucoma surgery was high (4.62%) in our study relative to rates previously reported in the literature. All patients, especially those with preexisting glaucoma, should be advised of the possible need for glaucoma surgery prior to undergoing treatment with the dexamethasone implant. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:680-685.].

Improving Outcomes for Patients With Diabetic Macular Edema.

Diabetic macular edema (DME) is one of the most common causes of vision loss in patients who have diabetes, and all of these patients are at risk for developing DME. The onset is often painless, difficult to detect, and can occur at any stage of diabetes. Ideally, DME is preventable, but treatment must be considered when preventative methods fail. Although physicians have several different treatment options for patients with DME, some patients who receive treatment can respond poorly and may even lose vision. Until recently, laser photocoagulation was regarded as the standard of care for DME; however, pharmaceutical treatments are rapidly replacing this standard as the desire to maximize systemic treatment of DME increases. A panel of experts gathered during the 2015 annual meeting of the Association for Research in Vision and Ophthalmology for a roundtable discussion designed to focus on improving outcomes for patients with DME using pharmaceutical treatment, including the use of anti-VEGFs and corticosteroids, based on the most current research and clinical data.

Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension.

PURPOSE: The pathophysiology of ocular hypertension (OH) leading to primary open-angle glaucoma shares many features with a secondary form of OH caused by treatment with glucocorticoids, but also exhibits distinct differences. In this study, a pharmacogenomics approach was taken to discover candidate genes for this disorder. METHODS: A genome-wide association study was performed, followed by an independent candidate gene study, using a cohort enrolled from patients treated with off-label intravitreal triamcinolone, and handling change in IOP as a quantitative trait. RESULTS: An intergenic quantitative trait locus (QTL) was identified at chromosome 6p21.33 near the 5' end of HCG22 that attained the accepted statistical threshold for genome-level significance. The HCG22 transcript, encoding a novel mucin protein, was expressed in trabecular meshwork cells, and expression was stimulated by IL-1, and inhibited by triamcinolone acetate and TGF-ß. Bioinformatic analysis defined the QTL as an approximately 4 kilobase (kb) linkage disequilibrium block containing 10 common single nucleotide polymorphisms (SNPs). Four of these SNPs were identified in the National Center for Biotechnology Information (NCBI) GTEx eQTL browser as modifiers of HCG22 expression. Most are predicted to disrupt or improve motifs for transcription factor binding, the most relevant being disruption of the glucocorticoid receptor binding motif. A second QTL was identified within the predicted signal peptide of the HCG22 encoded protein that could affect its secretion. Translation, O-glycosylation, and secretion of the predicted HCG22 protein was verified in cultured trabecular meshwork cells. CONCLUSIONS: Identification of two independent QTLs that could affect expression of the HCG22 mucin gene product via two different mechanisms (transcription or secretion) is highly suggestive of a role in steroid-induced OH.

Injection force comparison of the old and new dexamethasone implant insertion needles in porcine eyes and synthetic sclera.

BACKGROUND AND OBJECTIVE: Determine whether the new dexamethasone intravitreal implant (Ozurdex; Allergan, Irvine, CA) injector needle design can reduce the force needed for insertion when compared to the original needle design. MATERIALS AND METHODS: In vitro testing assessed the force required for insertion from five new-design and five old-design Ozurdex needles on a synthetic test medium and explanted porcine eyes. Maximum penetration force was measured in grams-force, while the total work of the needle was measured in joules. RESULTS: The new design required 29% and 68% less overall work to perform an injection in the synthetic medium (P = .0002) and porcine eyes (P = .009), respectively. The maximum force required to insert the new needle was 25% and 61% that of the old needle in the synthetic medium (P = .001) and porcine eyes (P = .007), respectively. CONCLUSION: The new needle design significantly reduces the force and work needed for insertion, which should improve physician control as well as patient safety and comfort.

Assessment of novel guarded needle to increase patient comfort and decrease injection time during intravitreal injection.

BACKGROUND AND OBJECTIVE: To determine whether a novel guarded 33-gauge injection device can make the intravitreal injection procedure faster and more comfortable for patients. PATIENTS AND METHODS: Single-center, prospective, randomized interventional study. Seventy participants receiving bilateral injections on the same day had one eye injected with the 33-gauge injection device without a speculum and the other eye injected with a standard 30-gauge needle using a speculum. Length of time needed for the injection procedure was assessed, and subjects were asked to complete a questionnaire regarding their comfort level with each device during the injection procedure as well as immediately after, later that evening, and the next day. RESULTS: Intravitreal injections using the 33-gauge injection device were significantly faster, but there was no significant difference in the incidence or levels of pain between the two needle types. CONCLUSION: The 33-gauge injection device may offer advantages over a standard 30-gauge needle when performing an intravitreal injection.

Increased incidence of sterile endophthalmitis after intravitreal triamcinolone acetonide in spring 2006.

PURPOSE: To compare the incidence of sterile endophthalmitis after intravitreal triamcinolone acetonide injections during a 6 month period in 2006 to the same period in 2005 and determine the incidence after switching to intravitreal preservative-free triamcinolone acetonide. METHODS: Retrospective multicenter interventional case series in which patients receiving intravitreal triamcinolone acetonide at three institutions from March 2005 to August 2005 and from March 2006 to August 2006 and intravitreal preservative-free triamcinolone acetonide from late summer 2006 through February 2007 were reviewed for the development of sterile endophthalmitis. RESULTS: From March 2005 to August 2005, the rate of sterile endophthalmitis was 0% at all institutions. From March 2006 to August 2006, a statistically significant increase in sterile endophthalmitis was seen at all institutions with frequencies of 3.5% to 6.3% (P < 0.001). With transition to preservative-free triamcinolone acetonide, sterile endophthalmitis over the next 6 months decreased to 0% at two sites and to 2.5% (from 5.5%) at the third institution (P < 0.009). CONCLUSIONS: A statistically significant increase in the rate of sterile endophthalmitis after intravitreal triamcinolone acetonide was seen in a 6 month period in 2006 when compared with the same period in 2005. Transition to preservative-free triamcinolone acetonide produced a frequency of sterile endophthalmitis similar to 2005.