has become a public health issue, with increasing prevalence in the United States, where more than 16 million people are affected.

 is a common and often chronic problem, particularly in older adults, younger populations are also being affected because of the increasing and constant use of digital devices.


	
	According to Audrey R. Talley Rostov, MD, the increased diagnosis of 

 among younger patients is increasing at an alarming rate, and parents should beware. 

developing in the pediatric population,” said Dr. Talley Rostov, who is in private practice at Northwest Eye Surgeons, Seattle.

With this in mind, it is more important than ever to establish effective treatments. 

“The goals of therapeutic intervention are normalization of the tear film, decrease lacrimal gland and ocular surface inflammation, stimulate epithelial healing, and restore the normal neural feedback mechanism to the lacrimal glands,” Dr. Talley Rostov pointed out.

and meibomian gland dysfunction, aqueous deficiency, evaporative goblet cell and mucin deficiency, exposure keratopathy, and co-conspirators. In dysfunctional tear syndrome all of these are not mutually exclusive and there often is overlapping. 
	
	

Top questions about MGD treatment options answered 

 is not new, but the addition of hypochlorous solutions used as lid scrubs is and they are beneficial. New topical antiparasitic drugs are available to treat Demodex. The in-office process of mechanical lid debridement has been improved with the introduction of an automated toothbrush-like device. In addition, more attention is being directed to the products used to remove make-up and the choice of cosmetics.

The treatment of posterior blepharitis, topical anti-inflammatory drugs, such as the off-label use of azithromycin, cyclosporine, and lifitegrast (Xiidra, Novartis); microwavable lid masks. Newer technologies such as thermal pulsation and intense pulsed light (IPL) are available, according Dr. Talley Rostov. 
	
	

Pinpoint underlying blepharitis, dry eye causes for best outcomes 

Thermal pulsation became available in 2011, and the technology has improved because of the introduction of several thermal pulsation devices. The devices are small, handheld, and less expensive. Studies have shown thermal pulsation to be efficacious with increased tear film break-up time and meibomian gland flow.

IPL, a non-laser light source that uses broad-spectrum light, destroys microvasculature and bacteria that introduce the inflammatory mediators to the meibomian glands and liquefies impacted meibomian glands. IPL has proven to be most successful for patients with advanced meibomian gland disease, telangectasias of the lid margins, and rosacea, according to Dr. Talley Rostov. 
	
	

 Determining where thermal pulsation + IPL therapy meet 

The newest approaches to improve lubrication of the ocular surface are ocular inserts and nasal neurostimulation, the latter of which involves internal and external electrical stimulation and pharmacologic nasal spray delivery that is in clinical trials. 

More artificial tears, some of which are oil-based, have become available; and ocular surface tears can be preserved with the reintroduction of scleral lenses. 

The real goal is treating the underlying inflammatory disease, which can be accomplished by using steroids, cyclosporine A, lifitegrast, autologous serum tears, amniotic membrane both cryopreserved and frozen, and omega 3.

Ocular surface inflammation: Vicious cycle of ocular surface disruption 

Evaporative goblet cell and mucin deficiency

With the goal of replenishing goblet cells, cyclosporine A is useful based on phase III studies, lifitegrast based on its anti-inflammatory effects, and compounded vitamin A ointment are the key innovations. Scleral lenses are also useful. 

Moist chamber goggles are an innovation in this area. However, patients also should take advantage of the tried-and-true treatments such as lubricating gel, lid tape, lid surgery, gold eyelid weights, and tarsorraphy.

A number of overlapping factors can be at work in dysfunctional tear syndrome that can exacerbate or masquerade as dry eye tear syndrome. These include superior limbic keratoconjunctivitis, topical medication toxicity, superficial punctate keratitis, mucous fishing syndrome, contact lens-related toxicity, chemical toxicity, allergic and atopic conjunctivitis, conjunctivochalasis, and floppy lid syndrome.

New anti-parasitic drugs are being investigated to treat Demodex, but are not yet approved.
	
	

This article is based on Dr. Talley Rostov's presentation at the Amererican Academy of Opthalmology 2019 annual meeting. Dr. Talley Rostov is a consult to Alcon, Allergan, Bausch + Lomb, and Novartis. 

Articles

New techniques probed for managing dry eye disease 

This article was reviewed by Andrea A. Tooley, MD


	
	According to Andrea A. Tooley, MD, 3D printing for 

 applications is not the future of ophthalmology. It is the present.

While ophthalmology has been slower than other medical specialties to adopt the 

applications of this technology, many applications are available, noted Dr. Tooley, an ASOPRS fellow at Columbia University and Manhattan Ear, Eye, and Throat Hospital, New York, and assistant professor of ophthalmology, Mayo Clinic, Rochester, MN.

3D printing is also known as additive manufacturing, in contrast to subtractive technology or the use of molds. The most common type of 3D printing is the liquid form, which uses thin layers of a liquid polymer that is cured rapidly by ultraviolet light to facilitate the addition of new overlying layers to create the desired shape. This is the primary use in medical applications and is referred to as stereolithography, Dr. Tooley explained.
	
	

Ophthalmology can 'adopt' technologies from other specialties 

Cardiovascular surgery, neurosurgery, orthopedics, and audiology are some of the medical areas that are taking advantage of the technology. However, she emphasized, 3D printing has a huge application in reconstructive surgeries as well as face transplantations.

Within ophthalmology, Dr. Tooley believes that the future may lie in 3D printed 

tools, and glaucoma drainage devices. Science fiction is becoming science fact. 

Researchers at Newcastle University, Tyne, U.K., have 3D-printed 

. For every person in the world who receives a 

 transplant, there are 69 others who still need one. As a result, more than 12 million people worldwide have limited sight due to a lack of eye donors. 

The research, led by Che Connon, PhD, and Steven Swioklo, PhD, developed the first 3D-printed cornea made with human cells. 

Doing justice to corneal irregularities 

models may be used outside of the operating room and are instrumental in 

Dr. Tooley noted that in complex cardiac cases, the exact patient anatomy can be 3D printed and then  can be used for practice before the actual surgery. Neurosurgeons can use the technology to prepare for complex aneurysmal repairs. She recounted that some cardiac surgeons are 3D printing their patients’ hearts and placing them inside a mannequin chest to establish the precise ergonomics they will encounter during the actual surgery.

“I believe that this has great potential for education in Ophthalmology,” she said. 

Dr. Tooley demonstrated a model of a 3D-printed orbit that she is currently using for a magnetic resonance imaging study of orbital tumors being performed at Columbia University, New York. Many universities, Columbia included, are now providing 3D printing free of charge for physicians.
	
	

New vitreoretinal tools advancing surgical outcomes 

Another application for the technology is the creation of 

 instruments. This approach could cut the costs of creating a prototype by an instrument manufacturer. Surgeons can then use the 3D printed instruments for practice in the laboratory and the instrument can be redesigned as needed. 

guides can be printed and used in the operating room. 

guides that are 3D printed not only decrease the time spent in the operating room, but they also improve 

Dr. Tooley also noted that 3D printing of 

 guides is especially important for orbital surgeries and craniofacial reconstruction. 
	
	

Are topical antibiotics needed after cataract surgery? Maybe 

“The scans of our patients can be custom used to create a 3D model of their anatomy or of the defect to be repaired and that model can be used in the operating room,” she said, describing a model used in a patient with a large orbital medial wall and floor defect resulting from removal of a tumor. 

“We were able to have a specific 3D printed guide that exactly matched the defect,” she said. “The titanium implant then could be shaped and modeled according to the 3D printed model, which reduces the time in surgery.”

Finally, customized patient implants are another possibility that can remain inside the patient.

These custom implants are used when transplanting a face from the donor to the recipient. Because this surgery demands absolute precision, cutting guides are printed and placed on the donor to indicate exactly where the cuts are to be made in the bone or tissue. This facilitates a perfect fit on the recipient.

Pearls to manage surgery patients on antithrombotic drugs 


	
	An example of another application was seen in the case of a patient with hemifacial microsomia. The surgeons were able to 3D print a custom implant that matched the normal side of the patient’s face. 

“It fit her anatomy and was symmetrical with the other side of her face,” Dr. Tooley reported.

The 3D printed materials also can be used in anophthalmic sockets. The printed implants perfectly match the defects in volume and anatomic requirements. 

Dr. Tooley concluded that some of the most exciting factors in 3D printing is bioprinting in which live cells are printed onto a live matrix. 

“This enables the building of an actual structure, such as ears or parts of the skull. That then can be implanted into patients,” she said. “In ophthalmology, the future is 3D printing of corneas or extra needed tissue. Even more imminent are customized 3D printed glaucoma valves or intraocular lenses. This is a tremendous technology that is at our fingertips.”
	
	

This article is based on Dr. Tooley's presentation at the American Academy of Ophthalmology 2019 annual meeting. Dr. Tooley has no financial interest in any aspect of this report. 

3D printing in ophthalmology 

The latest treatment option for endophthalmitis offers versatility and plasticity, is programmable for individualized drug delivery, and is 100% biodegradable. 

This article was reviewed by Irmgard Behlau, MD


	
	Various approaches have been developed to treat endophthalmitis, including topical and systemic drugs and periocular and intravitreal injections. The noninvasive methods of topical and systemic means of delivery are the goals because of their lack of invasiveness.
	
	With injections, there is always the risk of development of endophthalmitis. However, nothing is perfect and the holy grail remains elusive, according to Irmgard Behlau, MD.

According to Dr. Behlau, research assistant professor, Tufts University School of Medicine, Tufts Medical Center, Boston, drops work if the patient has kerato­endophthalmitis, but successful delivery is limited to only 1% to 7% of the drug. Frequent instillation every one to two hours is mandatory, and the drug has to get through the natural barriers of the ocular surface and tears.
	
	

Diagnostic advances offer glimpse of endophthalmitis pathogens 

Recent advances that have been achieved are antibiotics with small molecular weights, increased residence times and permeability, decreased toxicity, and slower degradation rates.

Dr. Behlau and colleague Joseph Ciolino, MD, explored an antibacterial-eluting contact lens that contained ciprofloxacin in one model and econazole in another model, both of which are small-molecule drugs. 

The ciprofloxacin-containing contact lens was a zero-order delivery system, and the econazole-containing lens demonstrated efficacy in the delivery of that antifungal drug.

One drawback to this is that producing such a treatment modality is burdensome and the question regarding how efficiently the drugs hit their targets remains unanswered, she explained.
	
	

Study targets therapies for endophthlamitis 

A mucoadhesive contact lens, developed by Prashad Garg, MD, was formulated from polyethylene glycol, glycerol, chitosan, and glacial acetic acid that contains moxifloxacin 0.4% and dexamethasone 0.1%. With a small burst, this contact lens achieved zero-order kinetics. 

A rabbit keratitis study showed that the moxifloxacin concentrations to the lens and cornea were high, but those in the aqueous and vitreous were wanting. 

“This result supports the notion that topical antibiotics do not work because they cannot penetrate to where they need to be. The concept of using them is not beneficial. The contact lenses provide better penetration, but the complexity and cost increase and the small molecules are limited,” Dr. Behlau stated.

Other approaches, including subconjunctivally, intracamerally, and transsclerally, are reliably unreliable.

Small changes can help beat the endophthalmitis bug


	In light of these short falls, all roads always seem to lead back to systemic administration, Dr. Behlau said, but it comes with a boatload of disadvantages. 

Providing access to drugs through the retinal pigment epithelium, Dr. Behlau explained, is confounded by the efflux pumps, P-glycans, and the multidrug resistant associated proteins. The back of the eye is inaccessible to systemically administered drugs. 

“The rule of thumb is that if the data show that a new drug can penetrate into the central nervous system, the drug often can penetrate into the eye; however, in order to access the eye, higher doses are needed and often intravenous administration.

The fluoroquinolones and linezolid can reach the eye when administered systemically, the latter of which may be useful for methicillin-resistant Staphylococcus aureus. Systemically administered antifungals are also useful for penetrating the eye.

Postop endophthalmitis rates similiar despite dissimilar practice patterns 


	Issues with this route of delivery are the sizes of the molecules injected and the elimination times. The route of elimination-anteriorly or posteriorly-affects the ocular retention time, with drugs eliminated anteriorly are retained longer. 

“The fluoroquinolones, for example, clear the eye posteriorly, which is why the drug has to be administered so frequently,” Dr. Behlau pointed out. 

It is also noteworthy that inflammation and pars plana vitrectomy increase the rate of elimination. For example, ciprofloxacin injected intravitreally remains in the eye for about 60 hours in an uninfected eye. In the presence of an infection, the drug is eliminated in about 16 hours.
	 

Are intracameral antibiotics the answer for endophthlamitis?


	There has been an explosion in the use of these drug delivery system, as evidenced by the drug-eluting contact lenses and intracameral implants, and in devices to treat age-related macular degeneration and diabetic retinopathy with direct delivery into the posterior segment, she explained.

According to Dr. Behlau, drug device combinations in many cases overcome the ocular barriers and elimination mechanisms.

“Anterior segment systems enhance the precorneal retention and tissue permeation,” she explained. “Posterior segment devices require sustained drug release to minimize the injection frequency.” 

Dr. Behlau pointed out that these devices are invasive and importantly carry the risk of foreign body infection.
	
	

Diagnostic advances offers glimpse of endophthalmitis pathogens 

An antimicrobial device implant is the first of its kind that can overcome some shortcomings of these drug devices is the antimicrobial silk ocular drug delivery implant that was designed by Dr. Behlau, Chiara Ghezzi, PhD, and David Kaplan, PhD , Biomedical Engineering at Tufts University, Boston, MA, for treating chronic posterior segment diseases. 

This implant is coated with N,N-hexy, methyl polyethylenimine to prevent infection, be biocompatible, and enable the zero-order sustained delivery of larger molecules, Dr. Behlau explained. 

This 4-mm to 5-mm device, with an inner diameter than can accommodate a 27-gauge needle, can be implanted without creating an incision. It also can retained in the eye in the pars plana as a result of its peanut shape. This device can stay in the eye for eight months without the need for an antibiotic.

“My hope is that this type of implant can be used to treat endophthalmitis over a long period of time and other diseases,” Dr. Behlau concluded. “This device has versatility and plasticity, it is programmable for individualized drug delivery and it is 100% biodegradable.” 
	
	

Dr. Behlau has no financial interest in any aspect of this report. 

Ophthalmology Times: Feb. 15, 2020

New techniques probed for managing dry eye disease

3D printing in ophthalmology

Seeking the holy grail treatment for endophthalmitis