Brad Barnett

Background: The Bimatoprost intracamerial implant (DURYSTA®) is currently only approved as a single-use device due to concerns of progressive loss of corneal endothelial cells following repeated intracameral administration. Currently depot systems such as DURYSTA® are placed in the anterior chamber, however the anterior chamber’s open environment allows for unrestricted movement of implants that results in corneal endothelial cell loss. Delivery of the implant to the posterior chamber may offer a means of providing similar or elevated levels of drug to the primary target, the ciliary body, while also isolating the implant from the cornea. This in turn may provide a means of safe serial administration. Materials and Methods: To assess migration after intracameral and posterior chamber DURYSTA® administration, a comprehensive analysis using a variety of imaging including optical coherence tomography, robotic ultrasound and slit lamp biomicroscopy video recordings were performed. Six patients (n=10 eyes) received a single DURYSTA® implant in the posterior chamber of one or both eyes. Intraocular Pressure (IOP) was measured after washout of all glaucoma medication at baseline, 1 week, 1 month and 3 months post-implantation. Paired t-tests, Cohen’s d and Hedge’s g compared each follow-up IOP to baseline. Finally, relative IOP lowering after posterior chamber administration was compared against reported IOP lowering in the ARTEMIS trials. Results: For posterior chamber implant imaging, only robotic ultrasound was satisfactory for DURYSTA® visualization. Robotic ultrasound confirmed that in ten pseudophakic eyes, the implant was held well positioned, sandwiched between the iris and pseudophakic lens complex. Mean baseline Average IOP was 24.9 ± 6.66 mmHg. Average IOP was recorded 16.4 ± 5.1 mmHg at 1 week, 13.1 ± 4.1 mmHg at 1 month and 15.2 ± 4.2 mmHg at 3 months. Paired t-tests revealed statistically significant reductions at all time points with confirmation of meaningful IOP lowering despite small sample size by Cohen’s d and Hedge’s g. IOP lowering by DURYSTA®, was found to be non-inferior with posterior chamber administration as compared to intracameral administration data from the ARTEMIS trials. Conclusion: Posterior chamber administration of DURYSTA® provided IOP lowering comparable to intracameral administration with no noted adverse events. ArcScan robotic ultrasound imaging confirmed stable implant positioning sandwiched between the iris and pseudophakic lens complex. This approach of delivery of implants to the posterior chamber merits further investigation as a novel implant location for ocular drug-delivery platforms to maintain efficacy while potentially reducing adverse events and opening up the possibility of serial administration.

Currently the bimatoprost implant (DURYSTA) is approved for a single administration secondary to concern for progressive corneal endothelial cell (CEC) loss with intracameral administration. In order to better understand the cause of CEC loss and other adverse events (AEs) with intracameral administration, multimodal imaging of the implant utilizing optical coherence topography (OCT), robotic ultrasound and bio microscopy video recording was utilized. Inherently the anterior chamber is a non-confined space. In certain examples the implant assumed a round and spotted structure as it picked up iris pigment as it migrated around the anterior chamber. Accordingly, we explored delivery of the implant in the middle segment behind the iris and in front of the pseudophakic lens. We then evaluated the suitability of various imaging modalities to assess the implant in this location. For middle segment administration, the ArcScan Insight 100 robotic ultrasound provided resolution and repeatability sufficient to monitor the implant behind the iris. This preliminary study hypothesizes that DURYSTA migration in the anterior chamber is the main source of AEs. Through use of a confined location, the middle segment, the implant is unlikely to migrate and cause CEC loss while also delivering drug closer to its site of action, the ciliary body. Further efforts are underway to understand the suitability of the middle segment for serial DURYSTA administration to maximize intraocular pressure lowering while minimizing AEs.

The term STODS (Surgical Temporary Ocular Discomfort Syndrome) has been coined to describe the ocular surface perturbations induced by surgery. As one of the most important refractive elements of the eye, Guided Ocular Surface and Lid Disease (GOLD) optimization is fundamental to success in achieving refractive outcomes and mitigating STODS. Effective GOLD optimization and the prevention/treatment of STODS requires an understanding of the molecular, cellular, and anatomic factors that influence ocular surface microenvironment and the associated perturbations induced by surgical intervention. By reviewing the current understanding of STODS etiologies, we will attempt to outline a rationale for a tailored GOLD optimization depending on the ocular surgical insult. With a bench-to-bedside approach, we will highlight clinical examples of effective GOLD perioperative optimization that can mitigate STODS’ deleterious effect on preoperative imaging and postoperative healing.

The term STODS (Surgical Temporary Ocular Discomfort Syndrome) has been coined to describe the ocular surface perturbations induced by surgery. As one of the most important refractive elements of the eye, Guided Ocular Surface and Lid Disease (GOLD) optimization is fundamental to success in achieving refractive outcomes and mitigating STODS. Effective GOLD optimization and the prevention/treatment of STODS, requires an understanding of the molecular, cellular and anatomic factors that influence ocular surface microenviroment and the associated perturbations induced by surgical intervention. By reviewing the current understanding of STODS etiologies, we will attempt to outline a rationale for a tailored GOLD optimization depending on the ocular surgical insult. With a bench to bedside approach, we will highlight clinical examples of effective GOLD perioperative optimization can mitigate STODS deleterious effect on preoperative imaging and postoperative healing.

Two months following penetrating keratoplasty for Acanthamoeba keratitis, a 76-year-old man was referred due to inability to wean high-dose topical steroids. Despite a very healthy graft and minimal pain, a scleral abscess involving three clock hours of the superior conjunctiva was present. The patient underwent conjunctival and scleral excision of the area of apparent infection with adjuvant mitomycin C and double freeze–thaw cryotherapy treatment followed by amniotic membrane graft. Recurrence was confirmed with PCR. Following a multimonth regimen of oral voriconazole and topical polyhexamethylene biguanide, chlorhexidine and moxifloxacin, the patient was weaned from all anti-infectious agents. After cataract surgery and scleral lens fitting, the patient is now 20/20 in the affected eye. This case highlights the need for judicious use of immunosuppressive agents as well as the necessary vigilance to monitor for recurrence with Acanthamoeba infection. It also represents the first reported use of adjuvant mitomycin C and double freeze–thaw cryotherapy for treatment of Acanthamoeba scleral abscess.

Purpose of review: The aim of this article is to review techniques to maximize all-distance uncorrected visual acuity and minimize photic phenomena after the implantation of multifocal and extended-depth of focus (EDOF) intraocular lenses (IOLs). This review examines the role of femtosecond laser-assisted cataract surgery (FLACS) in postoperative minimization of astigmatism and optimization of outcomes with multifocal and EDOF lenses. Recent findings: By incorporating intraoperative and preoperative imaging, femtosecond platforms such as those that utilize iris or conjunctival vessel registration, can enable a precision of corneal incisions and toric IOL markings that enable the lowest possible postoperative levels of astigmatism. Current studies suggest that with increasing IOL complexity, that is, trifocal versus bifocal, image degradation with even low levels of postoperative astigmatism are increased. To this end, current data support the utility of femtosecond laser arcuate incisions to enable the achievement of 0.5 D or less postoperative astigmatism for best outcomes with multifocal lenses. Summary: The synergistic combination of multifocal/EDOF IOLs with FLACS is an extremely promising route in achieving postoperative spectacle independence for patients. The marriage of the precision of FLACS with the increasing complexity of multifocal/EDOF IOLs will fuel nomogram adjustment and systematic improvements, such as the Wörtz–Gupta formula. Such strategies provide an unprecedented precision to cataract surgery that makes FOCUSED (Femtosecond Optimized Continuous Uncorrected Sight with EDOF and Diffractive Multifocal IOLs) a reality.

Purpose of review: to provide a prospective on the current mechanisms by which SARS-CoV-2 enters cells and replicates, and its implications for ocular transmission. The literature was analyzed to understand ocular transmission as well as molecular mechanisms by which SARS-CoV-2 enters cells and replicates. Analysis of gene expression profiles from available datasets, published immunohistochemistry, as well as current literature was reviewed, to assess the likelihood that ocular inoculation of SARS-CoV-2 results in systemic infection. Recent findings: The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2. In addition to direct ocular infection, virus carried by tears through the nasolacrimal duct to nasal epithelium represent a means of ocular inoculation. Summary: There is evidence that SARS-CoV-2 may either directly infect cells on the ocular surface, or virus can be carried by tears through the nasolacrimal duct to infect the nasal or gastrointestinal epithelium.

Purpose: Dupilumab, a monoclonal antibody directed against the interleukin-4 receptor subunit α (IL-4Rα) of IL-4 and IL-13, is increasingly being used to control atopic disease. Dupilumab use has been associated with a poorly understood conjunctivitis. In this study, we sought to investigate the hypothesis that dupilumab use and the associated IL-13 blockade causes a relative ocular mucin deficiency. Methods: Tear levels of mucin 5ac (Muc5AC) and total tear protein levels were evaluated from 28 eyes of 14 patients. Bilateral tear samples were acquired from seven patients on dupilumab and seven patients with no exposure to dupilumab. Study subjects were age and gender matched. In addition to tear samples, photographic documentation of ocular surface findings and a questionnaire of ocular surface symptoms were obtained. Between-group mean differences were calculated. Results: Compared with control, ocular Muc5AC levels normalized to total tear protein was statistically significantly lower. The average Muc5AC levels for persons on dupilumab was 1.54 ± 0.58 ng/mg and that of controls was 7.99 ± 1.16 ng/ mg. Persons on dupilumab reported a statistically increased occurrence of ocular fatigue/eye strain, uncomfortable sensation, pain, red eye, and itching. Conclusions: This study demonstrates for the first time, a relative deficiency of Muc5AC in patients on dupilumab. Translational Relevance: The results of this study support the previously reported role of IL-13 in increasing goblet cell density and associated Muc5AC production. Further efforts are underway to better understand the relative contribution of Muc5AC deficiency in the overall presentation of conjunctivitis associated with dupilumab use.