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Consistent trends across prevalence, incidence, odds and time-to-event models suggest ocular mitochondrial disease may indicate neurodegenerative risk

Eyeing the brain: How ocular mitochondrial disease may predict dementia risk

Rhino-orbital-cerebral mucormycosis, a life-threatening fungal infection, typically occurs in patients with diabetes

Fungal infection and vision impact in patients with diabetic eye disease

Ophthalmologists may be “at the forefront of a revolution in healthcare,” the nephrology professor said at this year’s International SPECTRALIS Symposium

Neeraj Dhaun, MD, PhD, says advances in OCT tech may positively impact patients with chronic kidney disease

New clinical guidance for anterior and posterior uveitis was published by a research team from the University of Bristol

Early uveitis detection and intervention is key to vision preservation, systemic health

The biomarkers are especially crucial for patients with lupus nephritis

Retinal microvascular changes in patients with systemic lupus erythematosus: Importance of OCTA 

In Fort Lauderdale, Florida, Dr Steven Yeh, dives into his presentation, “Front-line therapies and novel drug delivery for uveitis.” He outlines a few common therapies, such as methotrexate, mycophenolate mofetil (CellCept; Genentech), adalimumab, and fluocinolone acetonide via suprachoroidal delivery (Xipere; Bausch + Lomb).

I have the privilege, at the Retina World Congress, to speak to frontline therapies and novel drug delivery for the treatment of noninfectious uveitis. Within the field of uveitis, we're very excited about the different possibilities and the therapeutic alternatives in our armamentarium — both systemic therapies that have been shown through randomized controlled studies to be effective for the treatment of noninfectious uveitis. These include medications like methotrexate as well as mycophenolate mofetil, or CellCept, for the treatment of steroid-sparing agents for noninfectious uveitis. We also have level-one data related to adalimumab, which is a tumor necrosis factor alpha inhibitor, that's also helpful for the treatment of noninfectious uveitis.

Now, when we think about uveitic macular oedema, which is the leading cause of vision loss in uveitis, we also know this is very important to target these as well, both from the standpoint of reducing complications related to structural deficits as well as improving visual acuity.

And there have been other randomized controlled studies that have also looked at both intravitreal therapies as well as suprachoroidal drug delivery for the treatment of noninfectious uveitis. Within the realm of intravitreal therapies, the fluocinolone acetonide 0.18 milligram dose has been shown to be effective for reducing the rate of recurrences of uveitis in randomized controlled studies and two large phase 3 studies.

Now with regards to other treatments in uveitis, suprachoroidal drug delivery is a nuanced innovative drug-delivery platform that allows the treatment of macular oedema due to noninfectious uveitis. Xipere, which is administered via the suprachoroidal drug-delivery platform, delivers high levels of medication within the retina to the choroid for reducing levels to anterior segment structures. Within the PEACHTREE study, which evaluated suprachoroidal drug delivery compared to sham control, patients who received Xipere experienced a greater visual acuity gain with about 47% of individuals getting three lines or greater visual acuity over the 24-week endpoint. In addition, rates of cataract were comparable between sham control, as well as suprachoroidal drug delivery and intraocular pressure rates were favorable as well.

So, in summary, there's a lot to be excited about within the realm of treatment for noninfectious uveitis both within systemic therapies, we have randomized controlled studies with level-one evidence about their efficacy signals for the quality of life and the patient's visual acuity with noninfectious uveitis. And within the realm of local therapies, both intravitreal and via the superchoroidal route, there's a lot to look forward to with regards to drug delivery to improve visual acuity and the quality life of our patients.

 This transcript has been lightly edited for clarity.

Videos

Dr Steven Yeh provides a brief overview of available therapies for noninfectious uveitis and uveitis macular oedema.

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Noninfectious uveitis, uveitic macular oedema: A synopsis of frontline therapies

At Retina World Congress, Dr Harry W. Flynn presented a series of videos that illustrated vitrectomy techniques in endophthalmitis management cases. In the four cases he presented, Dr Flynn described a variety of endophthalmitis management options for retinal surgeons.

Thank you. I was part of a symposium on uveitis, and I was specifically talking about endophthalmitis management approaches. My focus was on vitrectomy techniques in the management of endophthalmitis cases.

I started out with a case of endogenous endophthalmitis caused by 

. The traditional way of handling these cases is to perform a pars plana vitrectomy. But many of these eyes are prone to retinal detachment because of vitreoretinal traction. And because of large lesions that have organisms growing through the choroid into the retina and into the vitreous, these lesions are often highly elevated.

In a video, I showed a technique of laser treatment to surround the lesions first, and then to actually obliterate the lesion with direct focal laser. We still use intravitreal and systemic antifungals as part of the treatment.

My second case was a bleb-associated endophthalmitis, and I show 27-gauge vitrectomy techniques to enter the eye, especially when these eyes are very congested, and to remove the vitreous and allow injection of intravitreal antibiotics. It is important to avoid de-bleeding the bleb because these blebs are highly necrotic. And if you do so, the debris mot will leave a large hole in the sclera often with leakage…very difficult to close. So we just use subconjunctival antibiotics in these cases, which are usually adequate.

My third video was on a combined approach to keratitis-associated endophthalmitis. These cases are particularly tough because the cornea is opaque. There is no view of fundus details. So I showed a combined approach with 25-gauge surgery, a corneal transplant, removal of the intraocular lens, performance of a pars plana vitrectomy, and placement of fresh corneal tissue graft in place when finally with injection of individual antibiotics.

My last case was a suture removal-related endophthalmitis. These cases occur rarely, but they do occur when people forget to use povidone iodine on the ocular surface. And these are often caused by 

 which is a very virulent organism, and it causes poor outcomes. I showed a technique of using 27-gauge vitrectomy in the anterior chamber to remove the fibrin clot, followed by a pars plana vitrectomy. again using 27-gauge techniques. The pictures that I showed were courtesy of David Jacobs, one of my former fellows who allowed me to use his slides.

In summary, I used my presentation as a way to present vitrectomy approaches for endophthalmitis in these very difficult and challenging cases.

Via four cases, Dr Harry Flynn describes a variety of endophthalmitis management options for retinal surgeons.

Approaches for managing treatment of patients with endophthalmitis

One of the worst things that can happen for a clinician is somebody with an infection, particularly if it's something you did surgery or you fit the contact lens. Whether it's a keratitis ophthalmitis, we really don't want it. And what we best want to do is treat it quickly and as best we can right away.

One of the things that I'm talking about today is the ARMOR study. It's a surveillance study in the United States of ocular isolates. We've been doing it since 2009, so we have data over a decade, and I'm specifically talking today about staph infections.

We saw over 3000 isolates of staph aureus, and nearly 2000 isolates of coagulase-negative staph, including Staph epidermidis.

We continue to see a significant amount of methicillin-resistant staph. So in the staph aureus side, it's changed a little bit, it did go down from 39%, to about 37%. And in the coagulase-negative side, it also went down — [it] was over 50%, now it's down to 37%.

The take home message for you — for us as clinicians — is that 40% of the staph, whether it's staph aureus, coagulase-negative staph, is methicillin-resistant.

Now, what does that mean? Well, if it's methicillin-resistant, when we test it against other antibiotics, it turns out to be multidrug resistant. So over 80% of the methicillin-resistant organisms are resistant to three other classes of organisms. So we really have to think carefully and wisely about how to pick an antibiotic.

The key thing is a patient comes in, we make the diagnosis pretty quickly, and we really want to get treatment started almost right away. Yes, we're probably going to get a culture or maybe even PCR to improve our diagnosis, but we really want to treat them right then and there. And that's where taking a look at the MICs, which is the laboratory way of looking at potency of antibiotics, really gives us some good information. ...

Obviously, you'll adjust your treatment depending on the culture results, resistance information that you get, but if we really want to get started right away, we'd have to pick an antibiotic.

I think the ARMOR study as a surveillance study of organisms in the United States is a great way to get your foot in the door as you begin treating these serious problems.

We look forward to sharing more information. This study is sponsored by B&L. I have no financial interest in the study, but I'm glad to share the results with you and look forward to sharing more results as we go forward.

Dr Penny Asbell discusses her presentation entitled, “Antibiotic Resistance among Ocular Staphylococcal Pathogens: Longitudinal Trends in the ARMOR Study."

ARMOR study: Evaluating antibiotic resistance in the treatment of staph infections

The PEARL [phase] 2 study was looking at the compound OC-02 in treating dry eyes. This is a nasal spray that is used twice a day.

Their primary endpoints were to look at increasing Schirmer's, as well as eye discomfort score. By using this nasal spray twice a day, in four randomized groups — so three different concentrations of OC-02 versus placebo — they found that the Schirmer scores were significantly higher in the drug arms, especially the highest drug concentration. And the eye irritation score was also improved most with the highest concentration of the drug.

This molecule is very similar to the OC-01 molecule, which has been FDA approved and marketed. This particular molecule, because of OC-01 being on the market already, is not going to be licensed in the US for marketing.

The take home message is that the use of the cholinergic agonists as a nasal spray to stimulate the trigeminal nerve is a reasonable mechanism to help treat dry eyes. It's novel; it's different than putting eyedrops in your eyes. It may be beneficial for patients who have trouble putting eyedrops in their eyes. A lot of people are used to using nasal sprays for allergies, for example. And so this modality of treatment, as well as a new mechanism, may have extensive benefits for the patients.

The study's primary endpoints were to look at increasing Schirmer's scores, as well as eye discomfort score.

Investigating efficacy of OC-02 to stimulate the trigeminal nerve for the treatment of dry eyes

Dr Raymond Douglas sat down to discuss his study analyzing the real-world adherence to teprotumumab (TEPEZZA; Horizon Therapeutics) as a treatment for thyroid eye disease (TED). While 90% of patients completed the therapy successfully, about 10% discontinued due to adverse effects. Investigators are digging into which of these effects are disrupting the treatment.

Dr Douglas is an board-certified aesthetic and reconstructive oculoplastic surgeon at Cedars-Sinai Medical Center. Dr Douglas contributed to the body of research that led to using teprotumumab as a treatment for TED. He continues to research the topic to improve adherence.

 Hi, I'm Raymond Douglas and I am from Cedars-Sinai Medical Centre, and we're based in Los Angeles. And today I was speaking about the real-world adherence for teprotumumab treatment.

And you know, it's really a fun study to do because we did the Phase 2 and Phase 3 clinical trials, which demonstrated the teprotumumab, reversed the proptosis, and improved patients and thyroid eye disease. But one of the things we really wanted to know is whether the adverse events and whether patients in the real world were following through on this therapy, the same way that they did in the Phase 2 and Phase 3 clinical trials. And so that was our poster today.

And the poster demonstrated that the adverse events were very similar to what we saw in the clinical trials in Phase 2 and Phase 3, which sometimes you don't see that in the real world versus clinical trials. And that over 90% of patients finished the whole course of therapy during this study period in time.

And there were dropouts, and there were adverse events reported and that led to these dropouts. But what was reassuring is that those were the same adverse events that we saw during the trial, which namely were muscle spasms, fatigue, nausea, some diarrhea, and those were the—accounted for the vast majority of adverse events that led to discontinuation.

So overall, you know, we were pleased to see that the real world is tending to coalesce with clinical trials—and how often does that happen?—but that 90% of our patients were actually able to finish these therapies, and there was very similar to what we saw in early clinical trials.

So the next step is to really look at and dive deeper into these adverse events. Because we want to know, you know, in those 10% of patients, we didn't know exactly which adverse event led to their discontinuation. We know that there was a group of them, but we want to know why and how we can help to overcome that [and] how we can help with any of the pain points that these patients are experiencing during their treatment.

This transcript has been lightly edited for clarity.

Dr Raymond Douglas discusses real-world adherence to teprotumumab as a treatment for thyroid eye disease.

Studying teprotumumab adherence in patients with thyroid eye disease

Dr Preeya Gupta, ophthalmologist at Triangle Eye Consultants, shares her four pearls for corneal collagen cross-linking.

Dr Gupta recommends that ophthalmologists manage patient expectations, monitor epithelial cells and warn about infectious keratitis. Because every patient is different, it is crucial that patients understand that their healing process may not look like another patient’s. Ophthalmologists may find clinical and interpersonal success when they see patients frequently postoperatively, according to Dr Gupta, because they can monitor how the epithelium is healing and counsel patients at the same time.

Well today I talked about corneal collagen cross-linking, which is a very important procedure in managing our patients with keratoconus. It has really been a sight-saving procedure to help halt the progression of keratoconus, which can be an extremely blinding condition.

The do's and don'ts: So we're talking about the FDA-approved protocol, which is the epithelial-off protocol.

I think my four pearls here are related to first and foremost setting expectations for our patients. Sometimes they think of cross-linking as a refractive procedure, which it can have refractive changes as part of it, but I like my patients to really think of cross-linking as a medical procedure that's really aimed at halting the progression of their disease.

I also think it's really important that patients understand that their vision can change for up to a year after this procedure. We certainly see patients that have reduction in their prescription, flattening of their cornea, and while I hope that for everyone, everyone comes out a little bit different.

Epithelial management is very important with cross-linking. Some of the potential complications of cross-linking include haze formation and infectious keratitis. So I think it's very important for clinicians to see their patients frequently postoperatively. And in those cases where perhaps the epithelium is not healing as quickly as we want, we know that these are abnormal corneas, often very steep corneas, which can make epithelial healing a difficult process for some patients. So we want to see them more often; we want to be aggressive about treating their epithelium.

I have a low threshold to actually remove the soft contact lens and place a cryopreserved amniotic membrane to accelerate the healing. I try to remove preservatives from the ocular surface, and then sometimes even lower the steroid dose initially to aid with epithelial healing.

Last but not least, infectious keratitis is something to consider. This is of course a dreaded complication of really any surgery. And so I have my patients stay on an antibiotic drop until re-epithelialization occurs, and I have a very low threshold to culture and you know, see my patient more frequently so that we can identify any infectious keratitis quickly and treat it.

Dr Preeya Gupta walks through her four pearls for successful corneal collagen cross-linking, including handling patient expectations, managing the epithelial cells and preventing infectious keratitis.

Corneal cross-linking and epithelial management: four pearls for success

Dr Penny Asbell discussed data from the ARMOR study with the editors of 

 at AAO 2021. The ARMOR study is a 10-year nationwide study examining in vitro antibiotic resistance among isolates that have been collected from ocular infections. The data sheds light on the effects of antibiotic resistance while treating ophthalmic infections, such as endophthalmitis.

The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has identified high levels of in vitro antibiotic resistance among ocular staphylococcal and pneumococcal pathogens, resistance that may affect treatment success.

Dr Asbell is the director of the Hamilton Eye Institute at the University of Tennessee Health Science Centre.

So, you know, ophthalmologists, we really like to get a lot of data. We take pictures, we take images, we take measurements. But with infection, we really got to start treating right away. And one of the questions is, what antibiotic should we start with?

So actually the ARMOR study, which is the only surveillance study done in the United States of ocular isolates, is a real good source of information when you're getting started.

So, we collect ocular isolates from over 44 sites and 22 states over the last 10 years. And in this particular study, we looked at isolates that were collected from either the aqueous, or the vitreous, presumably a patient who had serious infections such as endophthalmitis.

And what was most interesting is that nearly 50% of them were staph isolates that were methicillin resistant, so a high level of resistance to methicillin. But equally interesting is those methicillin resistant isolates, over 70% of them were resistant to three or more other groups of antibiotics. So you got to realize resistance is out there.

Now, this is laboratory testing. It's a standardized method. It's not actually clinical. In clinical, you might do a lot better than laboratory test suggests, but you got to start somewhere. It's a really good way of getting some information right off the bat, even while you're waiting for those cultures.

So think about resistance, it's not uncommon, whether it's staph aureus—we didn't see as much with strep pneumonia, and pseudomonas did pretty well, and so did the H. flu. But that staph still is a problem for us with the methicillin and the multi-drug resistance. So keep that in mind when you're picking an antibiotic.

So, you know, we've collected in the ARMOR study over 6000 isolates, and we're starting to try to understand what are the mechanisms of pathogenicity? What makes an isolate more serious than another isolate? And is it actually the isolate itself, or the interaction between the isolate, the organism, and its genetics and the person who gets infected?

So there's a lot of information there and a lot of opportunities to really understand infection more specifically, and maybe have new interventions for treating more effectively. So, we're gonna use that data to the best we can to give us the best information to be able to treat our patients the best way. So stay tuned for ARMOR data, we keep coming. Thank you for listening.

At the 2021 American Academy of Ophthalmology annual meeting, Dr Penny Asbell discussed data from the ARMOR study and its effects on treating ophthalmic infections, such as endophthalmitis.

Shedding light on antibiotic resistance in ophthalmology with ARMOR study data

Dr Christopher Starr of Weill Cornell Medicine, discusses an overview of his virtual ARVO 2021 presentation regarding dry eye disease flares, including a rapid readout assessment of 10 years' worth of world literature to analyze studies in which the inflammatory disease's condition are categorized.

Dr Christopher Starr discusses key points from his virtual ARVO 2021 presentation regarding dry eye disease flares, including a rapid readout assessment of 10 years' worth of world literature to analyze studies in which the inflammatory disease's condition are categorized.

Looking at 10 years of dry eye disease flares


John A. Hovanesian, MD, clinical instructor, UCLA Jules Stein Eye Institute, Laguna Hills, CA, discusses the highlights of his presentation titled "The D3 Study: Drug Delivery vs Drops — A Prospective Clinical Study Evaluating Dexycu vs Prednisolone Acetate 1% in Controlling Post-operative Pain and Inflammation in Patients Undergoing Sequential Cataract Surgery," during the virtual 2020 American Academy of Ophthalmology (AAO) meeting. 

John A. Hovanesian, MD, discusses the highlights of his presentation on a clinical study evaluating dexamethasone vs prednisolone acetate 1% in controlling postop pain/inflammation in sequential cataract surgery patients.

Controlling postop pain, inflammation in cataract patients: drug delivery vs drops


Prof. Giovanni Staurenghi, chairman of the University Eye Clinic, Department of Biomedical and Clinical Sciences at the University of Milan’s Luigi Sacco Hospital, Italy, discusses his presentation from this year's AAO, including findings from the HARBOR study of macular atrophy in AMD patients treated with ranibizumab.

Prof. Giovanni Staurenghi, chairman of the University Eye Clinic, Department of Biomedical and Clinical Sciences at the University of Milan’s Luigi Sacco Hospital, Italy, discusses findings from the HARBOR study of macular atrophy in AMD patients treated with ranibizumab.

Inflammation & Infection

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