Longitudinal Analysis of the Choriocapillaris Using Optical Coherence Tomography Angiography Reveals Subretinal Fluid as a Substantial Confounder in Patients with Acute Central Serous Chorioretinopathy Abstract Introduction To describe the influence of subretinal fluid (SRF) in analysis of the flow signal from the choriocapillaris (CC) via optical coherence tomography angiography (OCTA) in patients with acute central serous chorioretinopathy (CSC). Methods Observational, longitudinal, cross-sectional case–control study. Twenty-three eyes of 22 patients with acute CSC were compared with 20 eyes of 20 healthy controls. OCTA images (AngioPlex®, Zeiss) were recorded at baseline and follow-up examination and automatically quantified using an image-processing algorithm. Abnormal CC decorrelation signals (increased and decreased flow, IF and DF) were quantified using a custom image-processing algorithm. To analyze the spatial correlation between SRF and OCTA, CC signal heat-map images containing macular thickness information were used. Results Choriocapillaris flow alterations were significantly more pronounced at baseline than at follow-up examination in patients with acute CSC and resolving SRF (IF: p < 0.002; DF: p < 0.003). The extent of SRF correlated significantly with the abnormal CC decorrelation signals when comparing baseline with follow-up examinations (IF: rho = 0.56, p < 0.005; DF: rho = 0.64, p < 0.001). In particular, the reduced OCTA flow signal in the area occupied by SRF at baseline disappeared at follow-up examination (p < 0.02). In comparison with controls, CSC patients with complete resorption of SRF continued to show a reduced OCTA flow signal in the CC (p < 0.008). Conclusions The temporospatial association between SRF and reduced OCTA signal from the CC demonstrates that fluid might be a significant confounder for OCTA analysis in patients with CSC. CSC patients with complete absorption of the SRF at follow-up, however, show persistently reduced CC flow signals.

Sustained Control from Recurring Non-Infectious Uveitic Macular Edema with 0.19 mg Fluocinolone Acetonide Intravitreal Implant – A Case Report Abstract In January 2013, a 54-year-old pseudophakic woman was referred to the ocular inflammation clinic with a diagnosis of panuveitis, already on oral cyclosporine (100 mg/day) since 2010. She was a monocular patient, with the left eye eviscerated due to trauma and secondary endophthalmitis in 1995. She had experienced similar recurring episodes between 2010 and 2013. Examination revealed best-corrected visual acuity (BCVA) of 20/200. The anterior segment revealed the presence of flare and absence of cells. Intraocular pressure (IOP) was 11 mmHg. Fundus examination revealed the presence of anterior vitreous organization, exuberant cystoid macular edema (CME) and peripheral Dalen-Fuchs nodules with no activity. Systemic workup showed no changes, and a presumptive diagnosis of sympathetic ophthalmia was made. Initial therapy included topical and systemic corticosteroids. Cyclosporine was replaced with methotrexate (20 mg/week) due to nephrotoxicity. There was marked improvement in anterior inflammation and vitreous organization, but the ME remained exuberant (central ring thickness of 0.7 mm). Over the subsequent 4 years of follow-up, the patient received two intravitreous injections of a dexamethasone extended-release implant (Ozurdex®), with normalization of macular thickness and improvement in visual acuity (VA), but ME recurred around 6 months post-injection. During this period, the patient also underwent three sub-tenon injections of triamcinolone, with marked improvement of ME, but ME recurred between 4 and 6 months after treatment. She was thus recommended for treatment with a fluocinolone extended-release implant (ILUVIEN®). Post-implantation (3-year follow-up), she had controlled anterior inflammation without ME (central macular thickness of 248 µm). This case suggests that sustained control of inflammation enables better control of ME, and benefits may persist even after cessation of the direct anti-inflammatory effect of the implant. Funding Alimera Sciences Ltd funded the Rapid Service Fees.

Ophthalmic Outcome in a Belgian Cohort of Cystinosis Patients Treated with a Compounded Preparation of Cysteamine Eye Drops: Retrospective Analysis Abstract Introduction Treatment of the anterior segment problems in cystinosis is challenging as oral cysteamine is ineffective in the treatment of corneal problems because of its avascular structure. Although cysteamine eye drops have been formulated to counter this issue, the stability of cysteamine in these off-licensed formulations and treatment compliance are major problems. The aim of this retrospective study was to determine the efficacy of a compounded preparation of aqueous 0.5% cysteamine eye drops in the management of corneal complications of cystinosis. Methods Data of patients attending the multidisciplinary cystinosis clinic at the University Hospitals Leuven, Belgium between January 2015 and December 2018 were analyzed. All cystinosis patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops and oral cysteamine. Results A total of 12 patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops, of whom 75% were aged > 18 years (n = 9). The mean instillation frequency of the cysteamine eye drops was 3.3 drops/eye per day, and the mean number of hospital visits was two per year. All patients showed photophobia, > 30% corneal infiltration, blepharospasm, eye pain and conjunctival hyperemia during the study period. None of these symptoms improved with treatment with aqueous compounded 0.5% cysteamine eye drops. The corneal cystine crystal score was ≥ 2 in all patients at the last  visit. Conclusion Treatment with the compounded preparation of aqueous 0.5% cysteamine eye drops, combined with oral cysteamine, was not effective in reducing corneal cystine crystal deposition and other ocular symptoms in these patients with cystinosis. Funding Recordati Rare Diseases.

Optical Coherence Tomography-Based Deep-Learning Models for Classifying Normal and Age-Related Macular Degeneration and Exudative and Non-Exudative Age-Related Macular Degeneration Changes Abstract Introduction The use of optical coherence tomography (OCT) images is increasing in the medical treatment of age-related macular degeneration (AMD), and thus, the amount of data requiring analysis is increasing. Advances in machine-learning techniques may facilitate processing of large amounts of medical image data. Among deep-learning methods, convolution neural networks (CNNs) show superior image recognition ability. This study aimed to build deep-learning models that could distinguish AMD from healthy OCT scans and to distinguish AMD with and without exudative changes without using a segmentation algorithm. Methods This was a cross-sectional observational clinical study. A total of 1621 spectral domain (SD)-OCT images of patients with AMD and a healthy control group were studied. The first CNN model was trained and validated using 1382 AMD images and 239 normal images. The second transfer-learning model was trained and validated with 721 AMD images with exudative changes and 661 AMD images without any exudate. The attention area of the CNN was described as a heat map by class activation mapping (CAM). In the second model, which classified images into AMD with or without exudative changes, we compared the learning stabilization of models using or not using transfer learning. Results Using the first CNN model, we could classify AMD and normal OCT images with 100% sensitivity, 91.8% specificity, and 99.0% accuracy. In the second, transfer-learning model, we could classify AMD as having or not having exudative changes, with 98.4% sensitivity, 88.3% specificity, and 93.9% accuracy. CAM successfully described the heat-map area on the OCT images. Including the transfer-learning model in the second model resulted in faster stabilization than when the transfer-learning model was not included. Conclusion Two computational deep-learning models were developed and evaluated here; both models showed good performance. Automation of the interpretation process by using deep-learning models can save time and improve efficiency. Trial Registration No15073.

One-Year Outcomes of Second-Generation Trabecular Micro-Bypass Stents (iStent Inject) Implantation with Cataract Surgery in Different Glaucoma Subtypes and Severities Abstract Purpose To assess the 1-year efficacy and safety of the implantation of two second-generation trabecular micro-bypass stents (iStent Inject®) with concomitant cataract surgery in various subtypes and severities of glaucoma. Methods This single-surgeon, consecutive case series from a Canadian academic ophthalmology center included subjects with cataract, glaucoma, and the need to reduce intraocular pressure (IOP) and/or medications. The 12-month outcomes included mean IOP and medication burden as well as the proportions of eyes with IOP ≤ 18, ≤ 15, and ≤ 12 mmHg compared to baseline. Other measures included corrected distance visual acuity (CDVA), cup-to-disc ratio (CDR), visual field mean deviation (VF MD), retinal nerve fiber layer (RNFL) thickness, ganglion cell inner plexiform layer (GCIPL) thickness, and adverse events. Results In 118 eyes, mean IOP reduced from 17.00 ± 3.82 mmHg preoperatively to 13.97 ± 2.65 mmHg at the 12-month follow-up mark (17.8% reduction, p < 0.001), and mean medication burden decreased from 2.31 ± 1.33 preoperatively to 1.03 ± 1.10 medications (56% reduction, p < 0.001). After 12 months, 93% of eyes achieved IOP ≤ 18 mmHg (versus 69% preoperatively), 70% of eyes achieved IOP ≤ 15 mmHg (versus 42% preoperatively), and 29% of eyes achieved IOP ≤ 12 mmHg (versus 7% preoperatively). For all eyes, topical medications were either maintained or decreased from baseline, with ≥ 1 medication eliminated from the preoperative regimen for 83% of eyes and ≥ 2 medications eliminated for 36% of eyes. Visual acuity improved significantly, consistent with expectations for cataract surgery, while CDR, VF MD, and RNFL and GCIPL thicknesses remained stable. Safety was favorable, with no intraoperative complications and few transient adverse events postoperatively. Conclusion iStent Inject implantation with cataract surgery safely reduced IOP and medication burden in a real-world clinical population with mild to severe glaucoma, and stabilized visual field, as well as RNFL and GCIPL thicknesses on OCT. Funding The Rapid Service Fees were funded by Glaukos Corporation.

Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration Abstract Introduction Azithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil in the extraocular tissues, including the eyelid, and compared it with that of two commercial ophthalmic products, 1.5% levofloxacin ophthalmic solution and 0.3% ofloxacin ophthalmic ointment. Methods Rabbits were treated with either a single topical administration of 1% azithromycin ophthalmic solution, 1.5% levofloxacin ophthalmic solution, or 0.3% ofloxacin ophthalmic ointment. The eyelid, conjunctiva, and cornea were collected at 0.25, 0.5, 1, 2, 4, 8, and 24 h post-administration. Tissue samples were pretreated for drug concentration measurements by ultra-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis. Results Azithromycin was rapidly absorbed, and its levels remained near the observed maximum concentrations for up to 24 h post-administration in all tissue. In contrast, extraocular tissue concentrations of levofloxacin and ofloxacin decreased with time. The maximum concentrations of azithromycin, levofloxacin, and ofloxacin were 35.6, 34.1, and 55.1 µg/g in the eyelid, 44.2, 46.8, and 20.4 µg/g in the conjunctiva, and 79.9, 18.0, and 2.21 µg/g in the cornea, respectively. The values of the area under the curve from 0 to 24 h after administration of azithromycin, levofloxacin, and ofloxacin were 602, 58.5, and 267 µg·h/g in the eyelid, 837, 43.2, and 51.9 µg·h/g in the conjunctiva, and 1250, 26.4, and 5.46 µg h/g in the cornea, respectively. Conclusion The drug concentrations of azithromycin and levofloxacin were relatively comparable among the extraocular tissues following topical administration of the respective ophthalmic solutions, whereas the concentrations of ofloxacin varied following dosing of its ophthalmic ointment. The slow elimination profile in any extraocular tissue of rabbits was unique to azithromycin, and led to the demonstration of high exposures of azithromycin in all extraocular tissues after ophthalmic administration. Funding This research and Rapid Service Fees were supported by Senju Pharmaceutical Co., Ltd.

Management Issues in Conjunctival Tumours: Conjunctival Melanoma and Primary Acquired Melanosis Abstract Conjunctival melanoma is a rare malignant condition of the ocular surface. It is potentially lethal, with regional lymph node spread often preceding distant solid-organ metastasis. Due to its rarity and the long latency between treatment and local recurrence or the development of metastases, it is difficult to study. The literature is composed entirely of case series of varying quality, and there is significant variability in the management of this condition. This commentary attempts to distil the evidence base to provide practical management tips for the clinician.

Influence of Postoperative Posture on Macular Slippage after Macula-Off Retinal Detachment: A Randomized Controlled Trial Abstract Introduction To evaluate the effect of postoperative posture on the retinal shift after retinal detachment repair. Methods Patients who underwent pars plana vitrectomy (PPV) for macula-off rhegmatogenous retinal detachment (RRD) were included prospectively in the current study. Patients were randomized into two groups: group A included patients who did a log roll postoperatively, and group B included patients who had to lie flat on their backs for 6 h postoperatively before moving into the end position. Patients in group A and patients in group B were reviewed after 3 weeks and after 6 weeks, respectively, and fundus autofluorescence images (FAF) were obtained to visualize the retinal rotation. Results The sample included 50 eyes from 49 patients. Retinal shift occurred after RRD repair in 17 patients (34%). There was no statistically significant difference between the two groups (p = 0.94). Postoperative macular shift occurred significantly less often (p  = 0.049) in participants in whom heavy fluid was used in the procedure. Metamorphopsia was reported postoperatively by 10 of 17 patients with retinal shift (p < 0.001). Conclusion In our study, postoperative posture did not significantly influence postoperative macular slippage after RRD repair. The use of intraoperative heavy liquid appears to be associated with a lower occurrence of retinal shift.

Atropine 0.01% Eye Drops for Myopia Control in American Children: A Multiethnic Sample Across Three US Sites Abstract Introduction Topical atropine eye drops at low concentrations have been shown to slow myopia progression in East Asian studies. This study explored the effect of atropine 0.01% eye drops on controlling myopia progression in a multiethnic cohort of children in the USA. Methods A multicenter retrospective case–control study (n = 198) quantified the effect of adding nightly atropine 0.01% eye drops to treatment as usual on the progression of childhood (ages 6–15 years) myopia. Cases included all children treated with atropine for at least 1 year. Controls were matched to cases on both age (± 6 months) and baseline spherical equivalent refraction (SER) (± 0.50 diopters, D) at treatment initiation. The primary endpoint was the average SER myopia progression after 1, 1.5, and 2 years of therapy. A secondary outcome was the percentage of subjects with a clinically significant worsening of myopia, defined as a greater than − 0.75 D SER increase in myopia. Results The average baseline SERs for the atropine (n = 100) and control (n = 98) groups were similar (− 3.1 ± 1.9 D and − 2.8 ± 1.6 D, respectively) (p = 0.23). The average SER increase from baseline was significantly less for the atropine group than the control group at year 1 (− 0.2 ± 0.8 D compared with − 0.6 ± 0.4 D, p < 0.001) and at year 2 (− 0.3 ± 1.1 D compared with − 1.2 ± 0.7 D, p < 0.001). Secondary analysis at year 2 revealed that 80% of the control group vs. 37% of the atropine group experienced clinically significant worsening myopia of at least − 0.75 D (p < 0.001). There were no major safety issues reported in either group. Conclusion Similar to results reported in Asia, atropine 0.01% eye drops significantly reduced myopia progression in a cohort of US children over 2 years of treatment. Funding Nevakar, Inc. Plain Language Summary Plain language summary available for this article.

Real-world Case Series of iStent or iStent inject Trabecular Micro-Bypass Stents Combined with Cataract Surgery Abstract Introduction This real-world retrospective case series assessed 12-month effectiveness and safety following implantation of iStent® or iStent inject® trabecular micro-bypass with cataract surgery. Methods Consecutive patients were implanted with either iStent (comprising 1 stent) or iStent inject (comprising 2 stents), together with cataract surgery. Most patients had primary open-angle glaucoma. Effectiveness outcomes through 12 months included intraocular pressure (IOP) and glaucoma medications. Proportional analyses were completed for eyes achieving IOP ≤ 18 mmHg, IOP ≤ 15 mmHg, or IOP reduction ≥ 20% from preoperative; and eyes on 0 medications or ≥ 2 medications. Safety outcomes included adverse events, secondary surgeries, visual acuity, and visual fields. Results This analysis included 137 eyes (67 iStent, 70 iStent inject) with cataract and mild to moderate glaucoma or ocular hypertension. Over 73% of eyes in both groups had early disease, and ~ 22% had prior glaucoma surgery. At 12 months postoperatively, mean IOP decreased from 18.4 ± 4.2 mmHg to 14.2 ± 2.5 mmHg in iStent eyes (p < 0.0001), and from 20.4 ± 5.6 mmHg to 14.4 ± 2.1 mmHg in iStent inject eyes (p < 0.0001). The IOP reduction was significantly greater for iStent inject eyes than iStent eyes (6.0 mmHg versus 4.2 mmHg reduction, p = 0.034). Both groups had high proportions of patients achieving the 12-month IOP endpoints, although consistently greater proportions reached these endpoints after iStent inject than iStent: 95.7% versus 92.5% had IOP ≤ 18 mmHg, respectively; 74.3% versus 71.6% had IOP ≤ 15 mmHg, respectively; and 68.6% versus 62.7% had IOP reduction ≥ 20% from baseline, respectively. Mean medication burden at 12 months decreased from 1.8 ± 0.7 to 0.3 ± 0.5 medications in iStent eyes (84.0% reduction, p < 0.0001), and from 1.3 ± 0.9 to 0.1 ± 0.3 medications in iStent inject eyes (94.7% reduction, p < 0.0001). Significantly more iStent inject eyes were medication-free at 12 months than iStent eyes (92.9% versus 76.1% medication-free, respectively; p = 0.0068). Favorable safety included few adverse events, no secondary glaucoma surgeries, and stable visual acuity and visual fields in both groups. Conclusion Significant and safe IOP and medication reductions were achieved through 12 months after iStent or iStent inject implantation with cataract surgery. iStent inject eyes had greater absolute IOP reduction and more eyes medication-free versus iStent eyes. Funding Glaukos Corporation.