Procedure could prove to be alternative to trabeculectomy. 

This article was reviewed by Davinder S. Grover, MD, MPH


	
	The subconjunctival gelatin stent (Xen45 Gel Stent, Allergan) is a valuable addition to the glaucoma specialist’s surgical armamentarium because it provides a safe, effective and predictable means of creating a new pathway for aqueous humor drainage in eyes with an atrophic collector system, Davinder S. Grover, MD, MPH, said during the 2019 American Academy of Ophthalmology annual meeting.

“Trabeculectomy is not dead, but with the availability of this minimally invasive glaucoma surgery device that creates a new outflow system, I have significantly decreased the number of cases where I need to lean on trabeculectomy and expose patients to the risks associated with a conventional filtering procedure,” said Dr. Grover, attending surgeon and clinician, Glaucoma Associates of Texas, Dallas, TX. “With proper training and postoperative care as well as scar tissue modulation, the gel stent can safely and successfully help control IOP in a large number of refractory surgical glaucoma cases.”
	
	

Controlling adult glaucoma with cataract surgery, stent 

The stent is made of porcine gel crosslinked with glutaraldehyde. It measures 6 mm in length, has an outer diameter of 210 µm and an inner lumen diameter of 45 µm. In the United States, it is indicated for treatment of refractory open-angle glaucoma.
	
	The stent can be used regardless of glaucoma stage, and does not have to be combined with cataract surgery.

Traditionally, the stent has been placed in an ab interno procedure with delivery through a 1.8 mm clear corneal incision, but an ab externo approach performed through the conjunctiva or a small peritomy is possible, and the technique appears to be moving in that direction, Dr. Grover said. 

Presenting an intraoperative video, he provided this caution, “The surgery is not as easy as it looks, but with experience and proper training, it can be done well and provide a very safe and effective surgical treatment for glaucoma.”
	
	“One of the greatest technical challenges is becoming familiar with the ergonomics of the slider and injector used for the procedure.” 
	
	

Pearls to manage cataract surgery on hyptonous eyes 

Describing his personal ab interno approach, Dr. Grover said the implantation is done under topical anesthesia.
	
	He creates a 1 mm paracentesis in the superior temporal cornea, roughly 90° away from the planned main corneal incision through which he injects a high molecular weight cohesive viscoelastic (Healon GV, Johnson & Johnson Vision).
	
	Then he makes the clear corneal incision, and after rotating the globe inferiorly and drying the superior conjunctiva, places a mark 2 mm posterior to the limbus, as a guide to proper subconjunctival and intrascleral positioning of the stent. 

iStent implantation with cataract surgery 

“The device is 6 mm long, and in my experience, it ideally should lie 1 mm in the anterior chamber, 2 mm in the scleral wall, and 3 mm in the subconjunctival space,” he explained. Passing the needle tip of the injector system through the corneal wound can be a little difficult but a slight “shimmy” is helpful. 

Positioning and seating the needle in the superior angle is done under gonioscopic guidance. Dr. Grover noted that placing viscoelastic on the gonioprism is useful for maintaining good visibility. 

According to Dr. Grover, his goal is to seat the needle tip of the injector just slightly anterior to the trabecular meshwork. A key maneuver involves stabilizing the injector while delivering the stent to avoid a flick as the needle from the injector disengages from the scleral wall and retracts into the injector. 

“This was an initial hurdle for me,” he said. 

Once the injector has been fully inserted and the needle tip is tenting up the conjunctiva, Dr. Grover slowly advances the blue slider halfway to insert the gel stent in the subconjunctival space.  

“I want to exit right where the 2 mm mark is, and I want to be certain that it is in the subconjunctival space,” he said. “Perforation is possible, but it would be hard to do and is extremely rare.”  
	
	

Refractive considerations in cataract surgery in glaucoma patients 

If perforation occurs, the surgeon should simply bring the injector back into the anterior chamber, move the needle tip 1 to 2 clock hours to either side, and re-implant. 

“The small conjunctival perforation is usually small and does not leak, but make sure it is Seidel negative at the end of the case,” Dr. Grover said.

After implantation, inspection with gonioscopy should confirm that the implant is positioned away from the iris with proper proportions in the anterior chamber and subconjunctival space. 

“Using a blunt instrument or the back side of a cannula, the surgeon can roll away the chemosis, starting from the limbus towards to fornix, to flatten the conjunctiva and visualize the implant in the subconjunctival space,” Dr. Grover said. “You want to see that the stent is mobile and able to flap freely to the left and right, which is a sign that it is free of any obstruction and not imbedded in Tenon’s capsule.”
	
	

Surgeons share their experience of a new approach to gel stent implantation 

Undiluted mitomycin-C (40 to 80 Î¼g) is then injected subconjunctivally in the target quadrant away from the limbus, but first Dr. Grover said he injects a small bolus of 2% lidocaine to improve patient comfort.

“Because the procedure is done under topical anesthesia, patients will feel the burn of the mitomycin-C,” he explained. “A small lidocaine bolus has made a big difference for my patients and for me.”

A low bleb forms with the gelatin stent. Dr. Grover said that postoperative needling with mitomycin-C is needed in about 20% to 30% of cases. 

“Knowing how to needle and manipulate the bleb postoperatively is an essential component to success,” he said. “If the idea of a bleb or the need for postoperative manipulation scares you, my advice would be to ask yourself if this is a procedure that you want to learn.”
	
	

Bag-in-the-lens IOL reduces postop issues tied to previous models 

Data from the 510(k) pivotal trial that included 65 eyes of 65 patients showed that at 12 months, 75.4% of eyes had achieved IOP lowering from baseline of at least 20% while being on the same number or fewer medications.
	
	Mean baseline IOP was 25 mm Hg and it was reduced by an average of 9.1 mm Hg in the 52 patients who completed the 12-month followup. Mean number of medications was reduced by 50% from 3.5 to 1.7. There were no significant or unexpected complications.

Dr. Grover was lead author of the published article reporting the 12-month outcomes [Grover DS, et al. 

“In general, success rates over time in glaucoma surgery are in the 70-80% range, and so this is a very good result considering that the eyes in the study were very refractory cases with advanced disease,” he said.  

Innovations focusing on improved patient experience 

Dr. Grover said he uses the gel stent when angle surgery cannot be used, has failed, or is not expected to be effective. It can be effective if follow-up is difficult, for example because the patient has a long commute, is expected to be non-compliant, or needs to get back to work quickly; if a patient is on a blood thinner that cannot be discontinued for a few weeks; and when it is important to have a predictable refractive outcome.
	
	Dr. Grover added that he will not use it if there is active inflammation; extensive superior peripheral anterior synechiae; angle closure (unless the procedure is combined with phacoemulsification), neovascular glaucoma; an anterior chamber, unstable posterior chamber, or sutured

; or if the patient has iridocorneal endothelial syndrome or is expected to need penetrating keratoplasty. 

Dr. Grover provided a caution to consider facial anatomy because the presence of a prominent cheekbone and sunken eye may make surgery more challenging.

“In this situation, try to go as far nasal as possible,” he concluded.
	
	


	This article is based on Dr. Grover's presentation at the American Academy of Ophthalmology 2019 annual meeting. Dr. Grover is a consultant to and investigator for Allergan. 

Articles

Gel stent proves value in refractory OAG

Finding the sweet spot surrounding the number of anti-glaucoma medications translates to a balancing act with focus on individual patient needs. 

This article was reviewed by Janet B. Serle, MD


	
	Ophthalmologists have the luxury of choosing from among seven current IOP-lowering medications, with doses that range from one to four times daily. The list includes prostaglandin analogs (PGAs), rho kinase inhibitors, beta-blockers, alpha-agonists, carbonic anhydrase inhibitors (CAIs), miotics, and non-selective adrenergic agonists. 

This may well be an embarrassment of riches, with the ready availability of these options raising interesting questions and prescribing quandaries for physicians.

Likely the most important question is what is the optimal tolerated, effective, and reasonable IOP-lowering regimen? Janet B. Serle, MD, pointed out during a presentation at the 2019 American Academy of Ophthalmology annual meeting.
	
	

Looking behind IOP when managing glaucoma patients 

“We have a great deal of evidence-based facts about medical therapy,” she said. “We know that if a second, third, fourth, or more medications are added to a regimen, typically effective IOP reductions are not anticipated/obtained compared with when those medications are used as first-line interventions.” 

Dr. Serle, professor emeritus, Icahn School of Medicine at Mount Sinai, New York, noted that the duration of efficacy of a second, third, fourth, or more medications may be less and the efficacy tends to wane over time.

Other factors come into play that reduce patient compliance, such as regimen complexity, cost, side effects, age, physical infirmity, changes in mental status, education level, and health literacy. The nighttime efficacy is also less with some drugs, resulting in possible glaucoma progression. Inter-day and intra-day IOP fluctuations also can result in progression.

A study has suggested that combination therapy may actually reduce fluctuations. Chronic medical therapy causes changes in conjunctival tissue that may negatively impact incisional surgery, and chronic drug dosing contributes to ocular surface disease, Dr. Serle enumerated.
	
	

earls to manage surgery patients on antithrombotic drugs 


	While numerous caveats are related to the decisions to prescribe IOP-lowering medications, Dr. Serle noted that the question is what actually has been happening in medical practice.

A look-back at treatment practices shows a steady rise in the average numbers of medications prescribed over the past three decades. The average number in the Advanced Glaucoma Intervention Study in 1992 indicated that 2.7 drugs were prescribed.
	
	This was prior to the advent of the PGAs, topical CAIs, and adrenergic agonists. When those drugs became commercially available, the average number of medications rose to 3.0 and 3.2 in major studies from the late 1990s to 2004.
	
	By 2006, the average was 3.4, and the current regimens reported in peer review articles have included 3.6 medications; CME case reports have reported use of three to five medications in individual patients, Dr. Serle reported.
	
	

Tonometry can serve as tool in CME prevention 


	A few studies have provided positive evidence supporting the use of third and fourth drugs in the short term.

A small prospective Japanese study of ripasudil (Glanatec, Kowa Company, Ltd.), a rho kinase inhibitor with twice daily dosing, included 39 patients with a baseline of 3.6 medications; the study found that after 12 months of ripasudil treatment, there was an additional mean 15.5% decrease in IOP in more than two-thirds of patients.

A three-month retrospective study of netarsudil (Rhopressa, Aerie Pharmaceuticals) a rho kinase inhibitor approved in the United States, found an additional 3.9 mmHg IOP decrease in 172 eyes, that was similar in patients regardless of the number of baseline medications.
	
	

Reshaping medical treatment of glaucoma management 

A retrospective evaluation of brimonidine (Alphagan, Allergan) in 53 eyes also showed an additional 20% IOP decrease in 53% of patients after 12 months who had been receiving a mean of three baseline medications.

Many prospective studies of latanoprost (Xalatan and Pharmacia, Upjohn) have shown a positive additive effect of the drug, with IOP decreases ranging from more than 20% to 36% in patients taking multiple baseline medications, Dr. Serle reported.


	Fixed-dose combinations and co-drugs have changed the playing field in the past two years because, as Dr. Serle pointed out, they address all the caveats mentioned previously. To date, few studies of these drugs have been undertaken.

The question associated with these drugs, which include the co-drug nitric oxide-donating PGA latanoprostene bunod (Vyzulta, Bausch + Lomb), and the FDC netarsudil/latanoprost (Rocklatan, Aerie Pharmaceuticals), brinzolamide/brimonidine (Simbrinza, Alcon), topical CAI/beta-blocker (Cosopt, Merck Sharp & Dohme), and PGA/beta blocker (Xalacom, Pfizer), is whether the numbers of medications, bottles, or daily eyedrops should be counted, according to Dr. Serle.
	
	

Teleglaucoma lets patients be more engaged in care 


	Dr. Serle explained that when using the fixed-dose combinations, five medications can be instilled with four daily drop instillations, with only three bottles compared with previously when using pilocarpine alone, which was instilled four times daily. So, the consideration here is the level of individual patient tolerance for an ambitious regimen.

Patients can, she believes, instill three, four, or more topical medications daily, and in her practice some do so “reliably and comfortably.” 

If issues arise, the options include simplification of regimens or moving on to laser or surgery, she noted and pointed to a few red flags indicating when something other than medical therapy may be entertained: the promise of better performance by the patient, IOP variability from visit to visit, running out of or not filling prescriptions, and poor visit compliance.
	
	

Greater IOP-lowering potential with iStent inject 


	All things considered, the waters can be murky when it comes to deciding the number of medications to use in individual patients to delay surgery, Dr. Serle explained. Some data indicate that adding more medications results in additional IOP lowering, which may delay surgery in some patients.

Regarding the question about how much medication is too much, unfortunately, there is no magic number of medications or daily drops. 

“One patient’s sweet spot is another patient’s treatment burden,” she said, and the maximal number of medications that is effective, tolerated, and complied with varies markedly. The most efficacious and best-tolerated combinations of medications are unlikely to work for all patients. The bottom line seems to be highly individualized care.

“Make sure the target IOP is achieved, the disease is stable, and the patient is adhering to the regimen. These factors translate to the correct number of drop instillations daily,” Dr. Serle concluded.
	
	


	Dr. Serle is a consultant to Aerie Pharmaceuticals, Inc., Allergan, and Bausch + Lomb, receives grant support from Ocular Therapeutix and Allergan, and receives lecture fees from Aerie Pharmaceuticals, and Bausch + Lomb. She reported equity ownership in Aerie Pharmaceuticals. 

The Magnificent 7: How many glaucoma medications are too many? 

This article was reviewed by Bita Esmaeli, MD, FACS


	
	Clinical recognition of salmon patch infiltrate requires the consideration of a number of factors, and it is the first important step in diagnosing and managing conjunctival lymphoproliferative lesions including marginal zone B-cell lymphoma.
	
	Ophthalmologists should be familiar with the clinical appearance which is usually that of a “salmon patch” infiltrate and can affect any part of the ocular surface including the tarsal and palpebral conjunctiva.
	
	

This pathology is not limited to one area; the entire ocular surface must be inspected, according to Bita Esmaeli, MD, FACS, professor and director of the Ophthalmic Plastic and Orbit Program, at MD Anderson Cancer Center, Houston.

Eversion of the upper eyelid is important for identifying the full extent of conjunctival lymphomas. Some lesions, she explained, can be very small and limited to the caruncle or a small follicular infiltrate.

Symptoms can include chronic discharge, itchiness, conjunctivitis, and allergic reaction. In some cases, the lesions can be asymptomatic and discovered only coincidentally during the evaluation of other clinical processes.

SD-OCT may help diagnose primary vitreoretinal lymphoma


	Reactive lymphoid hyperplasia can have an appearance that is similar to lymphoma, indicating that biopsy is a key diagnostic step in ferreting out benign and malignant lesions, Dr. Esmaeli pointed out.

“Biopsy is required to establish the diagnosis of lymphoma and the exact histologic subtype,” she said.

Pathologists often rely on standard morphology, immunohistochemistry, and hematoxylin and eosin staining  in cases with conjunctival lesions because the tumor burden may be too small to facilitate flow cytometry, the gold standard for more definitive diagnosis of lymphoma, she pointed out.

Surgeons should also bear in mind that evidence of a lesion on the conjunctiva may be the proverbial tip of the iceberg, that is, the disease can extend well into the orbit. 
	
	

Exploring off-label, investigational approaches for allergic conjunctivitis 

“For conjunctival lymphoma, the histology is usually very low grade, and more than 90% are likely mucosa-associated lymphoid tissue (MALT) lymphomas,” Dr. Esmaeli said. “Other more aggressive histologic subtypes of lymphoma also can rarely occur, and in most cases they would have an extension into the orbit.”


	At this stage, an important goal is ruling out systemic lymphoma. Positron emission tomography-computed tomography are useful, as are bone marrow biopsy, which are performed at most cancer centers-and even “stage 4” conjunctival MALT lymphoma is possible to be found at initial diagnosis of conjunctival MALT lymphoma with a positive bone marrow involvement.

“That does not necessarily mean that patients need aggressive treatment, but it could be a clue that such patients with a positive bone marrow biopsy will relapse in the future at extraocular sites,” she said.
	
	

Read more clinical diagnosis content here 


	In cases of ocular surface lymphoma, probably more than 95% of patients undergo radiation therapy because the disease is characteristically low volume and low grade and in most cases does not extend past the ocular surface and is without systemic involvement.

“Radiation has served as the go-to treatment and the most practical solution for ocular surface lymphomas,” Dr. Esmaeli noted.

For the previous several decades, the current standard radiation dose for low-grade ocular adnexal lymphoma is 24 to 30 Gy delivered over two to three weeks, which is considered “low-dose” therapy. Dr. Esmaeli noted that this dose provides excellent local control in from 90% to 100% of cases. The late ocular morbidities include cataract development, mild keratitis, and dry eye in about 50% of cases.

More recently, an “ultra-low” dose of 4 Gy of orbital fractionated radiation that is administered in two sessions over two days has gained popularity and is currently being studied in a prospective trial at MD Anderson Cancer Center. 

Dr. Esmaeli reported that a retrospective analysis of the results in 23 eyes of 20 patients treated with the ultra-low-dose radiation resulted in responses in all patients, including complete responses in 13 patients (56%) and partial responses in 10 patients (44%) after a median follow-up of 14 months.
	
	These early observations were published in 2016. Based on the positive early observations, a prospective trial of the ultra-low dose radiation for orbital and adnexal low-grade lymphomas is underway at MD Anderson with the goal of recruiting 50 patients. 
	
	

aetiologies of paediatric conjunctival tumours

To date, 41 patients have been treated according to the protocol. When combined with the retrospective and off-protocol patients, a total of 70 patients have been treated. Advantages are short-treatment duration, lower cost, and lower ocular toxicity. The treatment also can be repeated if needed.

“We are very pleased with the results and this study may lead to a change in the acceptable dose of radiation delivered for low-grade lymphomas of the orbit and ocular surface,” Dr. Esmaeli pointed out, adding that the case of a patient treated in 2013 who responded well to the ultra-low treatment dose and had a prolonged treatment effect with follow-up in 2017. 

Other forms of treatment for lymphoma include chemotherapy, combined chemotherapy and radiation, immunotherapy, observation, and oral antibiotics, the last of which have no proven efficacy. These other treatment options may be needed in advanced stages  or high-grade lymphoma. 

“Clinical recognition of salmon patch infiltrate is the most important first step,” Dr. Esmaeli concluded. “The next step is biopsy to establish the histologic subtype of the lymphoma, which dictates treatment. Staging is vital. For stage 1E disease, very-low dose radiation, even 4 Gy, provides effective local control, convenience, and has low ocular toxicity.”
	
	


	Dr. Esmaeli has no financial interests in any aspect of this report. 

Ophthalmology Times: Nov. 1, 2019

Gel stent proves value in refractory OAG

The Magnificent 7: How many glaucoma medications are too many?

Casting a net to diagnose, treat cancerous lesions