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Another option for ophthalmologists, gelatin stent is found to lower pressure

 shunt was developed by AqueSys, which led to the company’s acquisition by Allergan in 2015. Not long after, the product was launched in Europe as the Xen transscleral gelatin stent.

The Xen stent is a 6-mm long hydrophilic gelatin stent, with an inner diameter of 45 micrometers.
	
	It is inserted with a preloaded injector, through a corneal incision, and exits into the subconjunctival space to form a bleb. Usually, mitomycin C is injected prior to stent insertion. 
	 

 Microinvasive glaucoma glaucoma surgery in children: Is there a role?


	The insertion can be performed as a standalone procedure or combined with 

. 
	
	In the United States, Xen is licensed as a treatment for refractory 

 in cases where previous glaucoma surgery may have failed or in cases that have become nonresponsive to maximum tolerated medical therapy.
	
	In Europe, however, the stent was launched for use as a primary surgical intervention that may prevent or delay the need for trabeculectomy and that can be performed at the same time as 

Hari Jayaram, MD, PhD, of the Glaucoma Service at Moorfields Eye Hospital in London, recently presented the results of a study of 7 years of data on surgical experience at Moorfields.
	
	The majority of the cases were of the second type mentioned above, as a primary intervention, which indicates that Xen is suited to primary open-angle glaucoma (POAG) when drops are not enough or previous medical treatments have failed.

Genetic variants linked with onset, progression of POAG


	The investigators performed a retrospective review of all ab-interno Xen procedures that had been performed at Moorfields.
	
	In extracting the data, they paid special attention to the patient’s ethnic origin and primary underlying diagnosis, their

and medication history over the time of follow-up, whether or not bleb needling had been performed, and whether or not the patient required further glaucoma surgery.
	
	They also looked at the incidence of complications, in particular hypotony and infection, as well as loss of vision. 

Failure was determined using a generous composite outcome, including an

 definition of less than 20% reduction of

 from the highest recorded pressure in the patient’s medical record, either with or without the use of eye drops.
	
	Outcomes measured included whether or not a patient was using drops, and failure also included reoperation for 

, endophthalmitis, or loss of light perception vision. Importantly, the need for bleb needling was not included among the criteria for failure. 
	
	

Pharmacologic treatment an option for treating glaucoma

The study looked at Xen insertions performed at Moorfields from May 2012 to June 2019. This included a total of 426 eyes from 375 patients.
	
	Five percent of the patients had undergone prior

. Almost two-thirds of the patients had an underlying diagnosis of POAG, and about a quarter had an underlying diagnosis of either uveitic glaucoma or another form of secondary open-angle glaucoma.

There was a wide age range of patients receiving the stents, from 16 to 95 years, with a mean age of 67. The patient population was typical of the ethnic diversity seen in London, with around 44% of patients coming from nonwhite British ancestry.  

Sixty percent of the cases were performed as standalone procedures and 40% were combined with 

 Mitomycin C was used almost universally. Some surgeons also used anti-VEGF treatments, and long-acting corticosteroid therapies. 
	
	

 Sustained-release implant offers long-term IOP control, preserved visual function


	The graph at left shows the long-term outcomes, using the above-mentioned definition for failure. At 1 year, 64% of the procedures were found to be successful. This reduced to 41% after 4 years.
	
	One interesting thing noted by the investigators is that almost a third of patients failed within the first postoperative year. 

Comparing standalone to combined surgeries showed no significant difference in the survival curve of the 2 groups. 

The researchers also looked at the impact of ethnicity. Patients of nonwhite British ancestry showed a trend in increase in late failure, but when viewed over the entire time course this did not reach statistical significance.
	
	The authors believe this is in keeping with the understanding that there is a more aggressive wound healing response in these ethnic groups. However, when successful, and further 

 was not required, patients with the Xen achieved a mean

The dropless future: SLT as a first-line treatment for glaucoma


	There was a mean reduction in medication use from 3 drops prior to surgery to about 1.3 drops over long-term follow-up in patients classified as successes.
	
	In terms of achieving drop independence, about 40% of patients who did not require further

 surgery were drop free beyond a 2-year period. 
	 


	Hypotony occurred in about 1 in 5 patients but responded well to conservative management. 

There was only 1 case of cleft formation that required surgical intervention. Bleb needling was very common, with 26% of patients needing at least 1 bleb needling procedure within the first 3 months after 

was the cause of failure in around a third of patients. Over half of these were revision procedures, which tended to be necessary early on in the postoperative course with a median time to reoperation of 4 months. 
	
	

Pearls for conducting GATT in open-angle glaucoma


	The overall infection rate was 1.6%. This is lower than that reported in the trabeculectomy group in the Tube Versus Trabeculectomy (TVT) Study (NCT00306852), which was 1.9%.
	
	However, it is higher than for all ocular

at Moorfields performed in 2018 (0.02%) and higher than the infection rate (0.3%) derived from annual core trabeculectomy outcome audits performed at the hospital.
	 


	The authors concluded that when stent insertion is successful, and further revision 

 is not required, the Xen stent can effectively lower pressure and reduce the need for medications.
	
	They noted, however, that surgeons should be aware of potentially high rates of reoperation and the long-term risks of bleb-related infection, and said that refining surgical technique and careful patient selection in the future may help optimize outcomes. 
	
	

Dr Jayaram has no financial disclosurers related to this content.

Minimally invasive glaucoma shunt delivers for patients

Research has found that chronic intravitreal injections may lead to ocular damage.

This article was reviewed by Richard Rosen, MD


	
	Intravitreal injections used to treat a variety of ocular diseases may contribute to progressive visual loss with chronic administration over years. One adverse event of intravitreal injections is acute transient increases in 

 that may increase the risk of damage to the macula and optic nerve over the long term. 

To underscore the importance of this issue and the numbers of patients at potential risk, Richard Rosen, MD, and colleagues pointed out that more than 6 million intravitreal injections were administered in the United States in 2016. Because these injections have been used for a relatively short period, the definitive consequences of chronic use remain to be determined.
	
	

Determining risk of ocular damage from chronic intravitreal injections


	
	A recent study reported that patients who received 7 or more intravitreal injections annually had an increased risk of undergoing glaucoma surgery.

Rosen is deputy chair for Clinical Affairs, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, the Belinda Bingham Pierce and Gerald G. Pierce Distinguished Chair of Ophthalmology, and director of Retina Services, New York Eye and Ear Infirmary of Mount Sinai, New York.

This happens, Rosen explained, because the injections cause the

 to elevate to 3 times the normal level. He noted that the IOPs return to normal within minutes of the injections, but he and his colleagues wanted to determine what the immediate impact is on the ocular blood flow. 

“Recently, we have become aware that repeated mild trauma to central nervous system structures, such as minor head bumps in athletes, can lead to degenerative brain injury with devastating results, decades later,” he said. “We wanted to better understand any potential risk for similar kinds of injury to the eye.”

Because of these concerns, Rosen, the senior investigator, and his team undertook a retrospective observational clinical study in which they measured retinal perfusion density changes on 

 angiography (OCTA) and thickness changes on OCT that were associated with acutely increased IOP after intravitreal injections.
	
	

OCTA a hope for diagnosing, managing ophthalmic diseases

The study, which included 40 eyes of 39 patients, was conducted at a tertiary care center in New York from October 2016 to June 2017.
	
	Patients were included who were 18 years and older, had vision exceeding 20/100, could fixate, had no media opacities, and were treated with bevacizumab (Avastin, Genentech, Inc) or aflibercept (Eylea, Regeneron Pharmaceuticals, Inc) to treat diabetic retinopathy (DR), retinal vein occlusions (RVOs), age-related macular degeneration, retinal neovascularization, or radiation retinopathy.
	
	The investigators analyzed the perfusion density on OCTA, thickness density on 

, and IOPs were measured before and after the injections were administered, Rosen recounted. 
	
	

OCT artifacts and pitfalls: In the eye of the beholder


	The patients, who were a mean age of 60.6 years, had a range of diseases, that is, proliferative DR (n = 9), age-related macular degeneration, and idiopathic polypoidal choroidal vasculopathy (n = 8) followed by central or hemispheric RVO (n = 6), radiation retinopathy, nonproliferative DR (n = 5 each), branch RVO (n = 3), and other (n = 3).
	
	The findings showed that various areas of the eye were affected differently by the IOP spikes. 

Alexander Barash, MD, clinical assistant professor of ophthalmology at The New York Eye and Ear Infirmary of Mount Sinai, and lead author of the study, reported finding significant (

 < .05) decreases in angiographic perfusion density in most areas of the superficial and deep layers on macular OCTA, except for the fovea.
	
	An average change of 7.5% was seen in the superficial macula and an average change of 2.4% in the deep macula. 
	
	

Subthreshold laser may reduce intravitreal injections for DME

< .05) decreases were seen in the OCTA perfusion density in the overall optic nerve head and the temporal and superotemporal aspects, with an average change of 3.3% in the optic nerve head.
	
	An average change of 2.9% was found in the radial peripapillary capillary layer that was preferential to the temporal region. 

The macular thickness seen on OCT decreased significantly (

 = .0312, respectively) temporally and increased nasally. Regression analysis showed relationships between age and decreased superficial macular perfusion. 

The IOP level before injections was only related to the 

 thickness in the fovea. The IOP change was related only to the decreased superficial macular perfusion density.

 = .018) associated with the overall decreased superficial macular perfusion. The investigators published their findings in 

The investigators commented that the decreased angiographic perfusion density “… that is associated with increased IOP likely contributes to the acute decrease in visual acuity experienced immediately after injections. Patients typically regain vision because the IOP decreases toward normal and blood flow returns to the macula.”
	
	

Preservative-free tafluprost/timolol lowers IOP well, glaucoma study shows

They also hypothesized that the increased OCT thickness nasally may result from redistribution of fluid or fluid shifts that occur when the IOP changes. 

“Doctors always have to weigh the benefits of any treatment with risks to the patient,” Barash said. “If we are inadvertently causing damage to ocular structures with our injections, we should make sure that all physicians performing the procedure are aware of possible [adverse events] so they can discuss these with patients and work to minimize the risks of these treatments.”

The investigators warned of the possibility that regular intravitreal injections may be sustaining perfusion-related injury to ocular structures that may produce glaucomatous damage to the macula and optic nerve.
	
	This newfound information can lead doctors to use advanced imaging and visual field testing to look for early signs of damage and perhaps lead to changes in the way ocular diseases are treated.

They suggested that the study results could pave the way for doctors to pretreat patients with medications to reduce the IOP spikes after receiving injections to prevent possible long-term damage.
	
	The investigators may also promote more careful consideration of the risks in patients with advanced glaucoma before administering injections. 
	
	

Dr. Rosen is a consultant to Optovue, Inc; Astellas Pharma; Boehringer-Ingelheim; Regeneron Pharmaceuticals; and Genentech-Roche. Dr Barash has no financial interest in this subject matter.

Eadie BD, Etminan M, Carleton BC, Maberley DA, Mikelberg FS. Association of repeated intravitreous bevacizumab injections with risk for glaucoma surgery. 

. 2017;135:363-368. doi: 10.1001/jamaophthalmol.2017.0059

Barash A, Chu TYP, Garcia P, Rosen RB. Acute macular and peripapillary angiographic changes with intravitreal injections. 

Study targets ocular damage from chronic intravitreal injections

Urinary bladder matrix, a skin substitute material made from porcine bladder, can be used successfully in periorbital reconstructive procedures.

This article was reviewed by Mark A. Alford, MD, FACS


	
	Urinary bladder matrix is a skin substitute material derived from porcine (pig) bladder used extensively in general surgery and to treat burns.
	
	The use of this product has now been extended to include periorbital reconstruction and is an effective alternative to granulation, skin grafts, or flaps in selected patients, according to Mark A. Alford, MD, FACS, an oculoplastic surgeon with North Texas Ophthalmic Plastic Surgery, Privia Medical Group, in Fort Worth.

“Our skin’s dermal extracellular matrix is a complex meshwork of proteins and carbohydrates, the main protein being collagen,” he said. “Collagen is supported by glycosaminoglycans and is woven together with proteoglycans and attached to cells with integrin and fibronectin.”

Alford explained these dermal components provide strength and structure to the skin and allow healing to take place.
	
	

Assessing the right angle: Surgeons getting back to basics


	The product (Cytal Wound Matrix and Micromatrix, Acell Inc) provides a source of naturally occurring growth factors, multiple types of collagen, laminin, fibronectin, proteoglycans, and elastin.

“Theoretically, the product acts as a bioscaffold that maintains and supports healing by facilitating remodeling of site-appropriate functional tissue to promote healing while preventing the development of scar tissue,” Alford said. “Studies have shown that the material decreases dermal fibrosis.”

Matristem is a xenograft, a material derived from animal tissue. Other commercially available xenograft materials include Integra Bilayer Wound Matrix (Integra LifeSciences Corp) produced from bovine collagen, shark, and silicone; OASIS Wound Matrix (Healthpoint Ltd) from porcine jejunum; and Matriderm (MedSkin Solutions Dr Suwelack AG) from bovine ligaments. 

In contrast, allografts, which are derived from human tissue, include products such as AlloDerm Regenerative Tissue Matrix (LifeCell) and Dermagraft (Organogenesis, Inc).
	
	

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Periocular reconstruction experience with the Acell matrix


	Alford’s initial experience included reconstructive procedures in 17 patients (11 women, 6 men), specifically, 14 with periocular Mohs defects, and 1 each with epidermolysis bullosa, cicatricial ectropion, and a skin graft donor site. The patients ranged in age from 36 to 84 years.

Alford described some illustrative cases. A 47-year-old patient had periocular epidermolysis bullosa refractory to conventional wound care over 2 years. Epidermolysis bullosa is characterized by a defect in laminin.
	
	Alford chose to use the ACell product because laminin is 1 of the glycoproteins supplied. The lesions healed after application of the urinary bladder matrix.
	
	

Use aesthetics to treat lid and periorbital conditions

Another case involved a 66-year-old patient with a large, superficial Mohs defect of the brow. At 6 weeks postapplication, the skin was completely healed and  eyebrow cilia were growing.

These patients showed significant improvement of their skin lesions. The ideal locations for use of ACell xenograft products are medial and lateral canthal defects, preauricular skin graft donor sites, and the superior rim and brow defects.
	
	Further experience with the material has shown that defects in the central lower eyelid need additional procedures such as lid lightening. Eyelid margin defects have not been studied.
	
	

Three-step surgery allays aging, fatigue in lower lid procedure


	Alford now has experience with more than 40 patients and has standardized his application protocol. The material is available as Cytal Wound Matrix sheets of various sizes and thicknesses and as MicroMatrix powder.

First, the powder is moistened with a small amount of sterile erythromycin ointment and normal saline to create a workable paste.
	
	After a sterile prep, the paste is used to cover or fill the defect and a 1-ply sheet of Cytal is sutured over the defect with a 6-0 chromic suture. The sheet is bolstered and patched for 2 weeks.
	
	After bolster removal, antibiotic ointment is applied to the area daily for 2 more weeks. A light dressing such as a bandage is used for protection. The procedure requires about 10 to 15 minutes.

Putting new technologies into practice not perfect science


	
	Alford reported that healing occurred with minimal scarring. No episodes of rejection, allergy, or infection have occurred.

“This is a quick and easy initial application, but close follow-up is required,” he said. “Even after 2 weeks of the bolster and patch, the defect looks ‘raw’ and patients need to be reassured. Most patients had some mild complaints about the long-term dressing.”

The retail cost of a 100-mg vial of powder is approximately $360 and a 3 x 3-cm 1-ply Cytal sheet is $86. The coding for the procedure is CPT 15275 (application of xenograft, eyelid) with a reimbursement of $150. Xenograft application is not bundled with other eyelid codes and can be used with other procedures.

“This product is fast, easy to use, and relatively inexpensive,” Alford concluded. “The procedure can be easily done in an office setting with local anesthesia and no sedation.” 
	
	

e: malford@txhealthcare.com
	Dr Alford has no financial disclosures related to this content.

Ophthalmology Times: June 15, 2020

Hieroglyphics eyechart

Minimally invasive glaucoma shunt delivers for patients

Study targets ocular damage from chronic intravitreal injections

Eyelid reconstruction: Urinary bladder matrix offers new xenograft for patients with large, difficult-to-treat lesions

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