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A letter to the editor is presented in response to the article "Bilateral Dacroadenitis Associated With Acute Crohn's Disease," published in the previous issue.

Purpose: To report on the imaging of internal limiting membrane (ILM) flap following macular hole (MH) surgery., Observations: Three eyes of 3 patients with baseline Snellen visual acuities (VAs) of 20/250, 20/30, and 20/100 underwent superior wide-base internal limiting membrane flap transposition (SWIFT) for MH. Indocyanine green (ICG) was used for intraoperative staining of the ILM. Following MH surgery, MH closed in all cases and VAs were 20/30, 20/30, and 20/60 respectively. An "en face" ICG fluorescence image of the ILM flap was obtained using infrared confocal scanning laser imaging at 795 nm. ICG fluorescence demonstrated the ILM flap to be intact and in good position with complete coverage of the MH in all cases. An area of hypofluorescence was present superiorly, corresponding to the flap harvest site with absent ILM. ICG hyperfluorescence of varying intensity was present at the MH site in all 3 cases. Folding of the ILM flap was present in one case., Conclusions and Importance: Following MH surgery, the status of an ILM flap may be evaluated by an "en face" image of the flap obtained by ICG fluorescence imaging. This imaging modality may be valuable in the study of various ILM flap techniques., (© 2021 The Author(s).)

Purpose: To analyze a series of eyes with brolucizumab-associated intraocular inflammation (IOI) without retinal vasculitis reported to the American Society of Retina Specialists (ASRS)., Methods: The ASRS Research and Safety in Therapeutics (ReST) Committee analyzed clinical characteristics from submitted reports of IOI after brolucizumab. Eyes with retinal vasculitis or that received intraocular antibiotics were excluded., Results: Forty-nine eyes of 45 patients were collected. Mean visual acuity (VA) at baseline was 20/49 (range 20/20 - 5/200). Patients presented with IOI a mean of 24 (range 3-63) days after most recent brolucizumab injection; 61% presented for an unscheduled visit while 39% presented at routine follow-up. Mean VA at IOI presentation was 20/67 (range 20/20 - 3/200). Most common symptoms were floaters (78%) and blurry vision (76%). Pain (20%) and redness (16%) were less common; 3 (6%) eyes were asymptomatic. IOI was anterior only in 18%, posterior only in 31%, and both anterior and posterior in 51% of eyes. Treatment included topical steroids alone in 67% eyes, while 10% eyes received no treatment. Mean VA at last follow-up was 20/56 (range 20/20 - 1/200). Three (6%) eyes lost 3 or more lines and 1 (2%) eye lost 6 or more lines., Conclusions: Brolucizumab-associated IOI without retinal vasculitis typically presented with a delayed onset of a few weeks. Often, visual acuity decline was relatively mild. Most symptoms resolved and nearly all had a return to baseline VA, but a small percentage of patients had a significant decrease in VA at last follow-up., Competing Interests: Declaration of Conflicting Interests Relevant potential conflicts of interest are reported as follows: AJW: none; PH: Genentech (Consultant, Lecture Fees), Allergan (Consultant); TGM: none; JFA: Springer SBM LLC (Patents/Royalties), DORC International B.V. (Consultant, Lecture Fees), Allergan Inc. (Consultant, Lecture Fees), Bayer (Consultant, Lecture Fees), Mallinckrodt (Consultant), TOPCON (Grant support); KJB: Bausch&Lomb (Consultant, Lecture Fees), Allergan (Consultant, Lecture Fees), Regeneron (Consultant, Lecture Fees), Novartis (Consultant, Lecture Fees), Genentech (Consultant); NC: Allergan (Consultant), Bayer (Consultant), Novartis (Consultant); GGE: Novartis (stock), Regeneron (stock); RAG: Genentech (Research, Speaker, Advisory), Regeneron (Advisory), Novartis (Research, Speaker, Advisory), Allergan (Research, Speaker, Advisory), Aerie (Research), Santen (Research), Graybug (Research), NovoNordisk (Research); SJK: none; JP: none; EWS: none; HT: Alimera (stock); RWW: Novartis (Research)

Purpose: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration., Methods: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab., Results: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied., Conclusions: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown., Competing Interests: Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Relevant potential conflicts of interest are reported as follows: A.J.W.: none; P.H.: Genentech (consultant, lecture fees) and Allergan (consultant); T.G.M.: none; J.F.A.: Springer SBM LLC (patents/royalties), DORC International B.V. (consultant, lecture fees), Allergan Inc (consultant, lecture fees), Bayer (consultant, lecture fees), Mallinckrodt (consultant), and TOPCON (grant support); K.J.B.: Bausch&Lomb (consultant, lecture fees), Allergan (consultant, lecture fees), Regeneron (consultant, lecture fees), Novartis (consultant, lecture fees), and Genentech (consultant); N.C.: Allergan (consultant), Bayer (consultant), Novartis (consultant); G.G.E.: Novartis (stock), and Regeneron (stock); R.A.G: Genentech (research, speaker, advisory), Regeneron (advisory), Novartis (research, speaker, advisory), Allergan (research, speaker, advisory), Aerie (research), Santen (research), Graybug (research), and NovoNordisk (research); S.J.K.: none; J.P.: none; E.W.S.: none; H.T.: Alimera (stock); R.W.W.: Novartis (research).

Purpose: To report on the technique of scleral fixation of fluocinolone acetonide (FAc) implant in 2 eyes with recalcitrant diabetic macular edema (DME)., Observations: Two eyes of 2 patients with persistent DME, partially responsive to anti-VEGF therapy, underwent intravitreal FAc implant injection. First case had a history of pars plana vitrectomy (PPV) and scleral fixated posterior chamber intraocular lens implant (PCIOL) for retained lens fragments and dislocated IOL. Subsequently, the patient presented with intermittent anterior chamber migration of the FAc implant associated with an increase in DME. The FAc implant was fixated to the sclera, preventing further migrations, and improving the DME. The second case had a history of persistent DME, PCIOL with open capsule, epiretinal membrane (ERM), and a free-floating FAc implant within the vitreous cavity. She underwent PPV, membrane peel, and simultaneous scleral fixation of the free-floating FAc implant. The surgical technique included 23 G PPV, externalization of FAc implant, re-implantation and scleral fixation through the same sclerotomy utilizing a 10/0 prolene suture., Conclusions and Importance: A surgical technique for scleral fixation of FAc implant is described. The technique is valuable in the management of patients with persistent diabetic macular edema or uveitis who benefit from treatment with fluocinolone acetonide implant but are at risk for anterior chamber migration of the implant., (© 2020 Published by Elsevier Inc.)

This study was performed to achieve sustained-release Ibuprofen matrix tablets with a zero-order release kinetic while most of the previous formulations have shown Higuchi release kinetic. Considering the results from previous studies, ethyl cellulose, Carbopol 934P, Carbopol 974P, and Pemulen TR-1 were used at different amounts for preparation of the tablets by direct compression. The release profiles were studied in a two-stage release test using non-linear regression analysis. Carbopols 934P and 974P could not sustain the release adequately while Pemulen TR-1 had too strong sustaining effect. Therefore, combination formulations were considered and studied. The release profiles of ethyl cellulose formulation and the combination formulation consisting Carbopol 934P and Pemulen TR-1 best fitted in Higuchi model, although the zero-order model was not completely rejected. However, the kinetic model of release from the combination formulation consisting Carbopol 974P and Pemulen TR-1 changed to zero-order indicating the most constant release rate among formulations. This was speculated to be due to some erosion of the gel, as well as some interaction of the hydrophobic chain of Pemulen TR-1 with Ibuprofen. Therefore, this formulation is suggested for directly compressed sustained-release matrix tablets of Ibuprofen with a more constant release rate.

Vitamin E (α-tocopherol) is a natural antioxidant very useful for preventing the harmful effects of UV sun rays as skin aging and cancers. In this study, different MLV formulations were made using egg lecithin and varying molar ratios of α-tocopherol and/or cholesterol, and their encapsulation efficiencies were determined. The best liposomal product was incorporated into a carbomer 980 gel. The resulting preparation was then studied with regard to the rheology and release profile using r(2) values and Korsmeyer-Peppas equation. The encapsulation efficiency was dramatically decreased when using α-tocopherol at molar ratios of 1:10 or more, which is suggested to be due to the defect in regular linear structure of the bilayer membrane. Addition of cholesterol to formulations caused a decrease in encapsulation efficiency directly related to its molar ratio, which is due to the condensation of the bilayer membrane as well as competition of cholesterol with α-tocopherol. The liposomal gel showed a yield value of 78.5 ± 1.8 Pa and a plastic viscosity of 27.35 ± 2.3 cp. The release showed a two-phase pattern with the zero-order model being the best fitted model for the first phase. However, the "n" and r(2) values suggested a minor contribution of Higuchi model due to some diffusion of α-tocopherol from the outermost bilayers of the MLVs to the gel. The second phase showed a non-Fickian release indicating a more prominent role for diffusion. This combinational release profile provides a high initial concentration of α-tocopherol followed by a slow release throughout a 10 h period.

Objective: Observational data, though sparse and based on small studies with limited ability to control for known breast cancer risk factors, support a lower risk of breast cancer in blind women compared to sighted women. Mechanisms influenced by ocular light perception, such as melatonin or circadian synchronization, are thought to account for this lower risk., Methods: To evaluate whether blind women with no perception of light (NPL) have a lower prevalence of breast cancer compared to blind women with light perception (LP), we surveyed a cohort of 1,392 blind women living in North America (66 breast cancer cases)., Results: In multivariate-logistic regression models controlling for breast cancer risk factors, women with NPL had a significantly lower prevalence of breast cancer than women with LP (odds ratio, 0.43; 95% confidence interval, 0.21-0.85). We observed little difference in these associations when restricting to postmenopausal women, non-shift workers or when excluding women diagnosed with breast cancer within 2 or 4 years of onset of blindness. Blind women with NPL appear to have a lower risk of breast cancer, compared to blind women with LP. More research is needed to elucidate the impact of LP on circadian coordination and melatonin production in the blind and how these factors may relate to breast cancer risk.

Purpose: In this study, the authors sought to develop and characterize techniques for measuring changes in choroidal neovascularization (CNV) lesion size and fluorescence over time for quantitative analysis of fluorescein angiograms., Methods: Initial assessment of the quantitative technique was made by retrospectively analyzing digital fluorescein angiograms taken before and 3 months after photodynamic therapy (PDT) for CNV (6 patients, group 1). The method was then applied prospectively to digital fluorescein angiograms (baseline and day 71) obtained on 12 patients taking part in a clinical trial investigating the effect of vascular endothelial growth factor (VEGF) Trap in CNV (group 2). Two masked observers, with the use of image processing, measured the area of hyperfluorescence and fluorescence intensity above background. Values for each image were plotted against time after dye injection to generate curves, and each area under the curve (AUC) was calculated., Results: The physician who treated the patients in group 1 judged the condition of three patients to be improved and of three to be worse 3 months after PDT. Masked retrospective grading of fluorescein angiograms showed an 11% decrease in AUC for fluorescence area and a 32% decrease in AUC for fluorescence intensity in the three patients whose conditions clinically improved but increases of 131% and 292% in the three patients whose conditions clinically worsened. In group 2, a 38% decrease in AUC for fluorescence intensity and a 19% decrease in AUC for fluorescence area were observed in patients who received VEGF Trap compared with increases of 66% (P = 0.004, Mann-Whitney U test) and 21% (P = 0.07) for patients who received placebo. Macular volume decreased by 11% in VEGF Trap-treated patients and increased by 10% in placebo-treated patients (P = 0.03)., Conclusions: This study reports a technique for analysis of change in fluorescence area and intensity over time during fluorescein angiography (FA) using a continuous scale and its application in a clinical setting and a clinical trial. Compared with previous techniques making use of categorical scales, this approach provides an advantage for evaluating responses to treatment that may improve the value of FA as an outcome measure in clinical trials.

Medical audit is now a well-established part of the routine of ophthalmology departments. Accomplishing a complete audit is a complex task and its effectiveness depends on how it is performed. In order to evaluate the procedure in our department a retrospective analysis of 18 audits was carried out with particular reference to the level, objectives, beneficial effects, and effects on current practice. Our practice was critically analysed using these factors. One audit fulfilled the criteria for a full audit. Eleven (60%) were partial or potential and six (30%) were an attempt in planning an audit. The majority omitted plans for implementing change or targets for future assessment. Seven had educational benefit. There was little effect on patient care, cost-effectiveness or communication. Medical audit can be clinically effective, educational and stimulating. Failure to complete all stages affects the outcome. This study identifies the difficulties involved in performing complete audits and suggests improving the procedure by auditing audits on a regular basis.

Following cataract surgery, entrapment of the iris within the surgical wound is often managed by intensive use of miotics. As the radial fibres stretch, only a small amount of fraction is exerted upon the entrapped iris. Application of a combination of phenylephrine and pilocarpine drops causes simultaneous contraction of the pupil sphincter and the radial muscle fibres. This study investigated the relative magnitude of forces induced in the iris periphery by pilocarpine and phenylephrine and the effectiveness of adding g. phenylephrine 10% to g. pilocarpine 4% drops in the treatment of postoperative irido-corneal adhesions. The investigation was divided into two parts. First, the forces induced in the iris periphery upon exposure to pilocarpine and phenylephrine were measured in 6 cadaver irises. The mean force was 27.5 +/- 5.7 x 10(-3) N for pilocarpine and 23.3 +/- 4.0 x 10(-3) N for phenylephrine. The combination of the two drugs produced a force of 54.2 +/- 6.6 x 10(-3) N (p < 0.05). In the second part of the study intensive pilocarpine 4% drops were administered to 17 patients who had iris-wound entrapment on the first post-operative day. Patients with persistent adhesion were commenced on intensive g. phenylephrine 10% and assessed after 90 minutes. Of the 17 patients, 6 responded to pilocarpine drops alone; in a further 7 the irido-corneal adhesion was released only by the addition of phenylephrine drops, and in 4 patients drops were ineffective in relieving the adhesion. This study indicates that addition of phenylephrine 10% to pilocarpine 4% drops enhances the effectiveness of pharmacological treatment of post-operative irido-corneal adhesion.