Lynda Charters

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Reviewed by JosÃ© Luis Tovilla-Canales, MD


	
	Upper eyelid blepharoplasty (UEB) is the most frequently performed invasive facial esthetic procedure, according to

. The procedure can remove excess skin, muscle and sometimes fat from the upper or lower eyelids. It is performed for either functional or cosmetic indications. UEB may be performed in a traditional fashion, using stainless steel instruments, or may be modified with radiosurgery incisional techniques or laser incisional techniques.
	
	Following UEB, the visual fields can improve by as much as 26.2%. Dr. Tovilla-Canales, director, 

Orbit and Oculoplastics Department, Instituto de Oftalmologia, Mexico City, Mexico

, enumerated his pearls for performing a successful UEB. “The surgery is usually considered a simple procedure, but there are key points that must be adhered to before surgery to avoid adverse events,” he said. Dr. Tovilla-Canales offered several key points to consider for successful UEB procedures:

The procedure is not a recipe. Each patient will have different anatomic landmarks, and, therefore, have different surgical needs.

The brows and the different amounts of skin to be excised must be considered.

Understand the anatomy. Knowledge of the anatomy is essential to perform an appropriate technique for each patient.

The preoperative assessment is one of the most important steps before surgery is even undertaken. The physician must obtain a history and perform a complete examination, discuss expectations with the patient, select the appropriate technique, and discuss potential complications.

Patients must be instructed to stop taking aspirin and anticoagulants before surgery.

 Physicians also should obtain preoperative photographs in the event that patients question the postoperative outcome.

Another consideration in the preoperative assessment is determining whether just skin or skin and fat are to be removed.

“Watch the eyebrow,” Dr. Tovilla-Canales said, pointing out that the eyebrows are always considerations when performing UEB. He demonstrated cases with the preoperative presence of upper lid ptosis, a droopy eyebrow, fat pads in the lateral aspect upper lids disguised as upper lid ptosis and bulging of the upper lids caused by supraobicularis fat, indicating that these must be addressed to achieve an appropriate UEB.

Perhaps the most important surgical factor is marking the incisions, according to Dr. Tovilla-Canales.
	
	“With the patient supine, I create the crease in the patient’s natural crease, usually 10 millimeters from the lid margin in women and a little lower in men,” he explained, demonstrating the pinch test, performed using forceps with the patient sitting and with eyes closed, to determine the amount of skin to remove.
	Dr. Tovilla-Canales said he uses a guideline of 20 millimeters from below the incision to above the incision as a safe amount. When it comes to anesthesia, Dr. Tovilla-Canales advises administering intravenous sedation preoperatively and a small amount of local anesthesia.
	
	The incision, skin and fat removal also are important, and Dr. Tovilla-Canales said his preference is to create incisions using a blade rather than a CO2 laser because of the possibility of wound dehiscence related to the laser. Once the incision is created, Dr. Tovilla-Canales performs electrocautery. When removing the orbicularis, he said he prefers to remove only skin and preserve as much orbicularis as possible.
	
	When removing fat, he extracts the least amount possible to avoid hollowing of the eye. Typically, he removes only the medial fat pad. Dr. Tovilla-Canales also emphasized the importance of identifying lacrimal gland prolapse, which also can mimic the appearance of fat pads; his procedure of choice in such cases is to reposition the lacrimal gland with sutures.
	
	The procedure is not simply one of removing skin and/or fat, but recognition of structural issues such as ptosis. “Surgeons must be very conservative with the amount of skin, fat, and orbicularis muscle that is left postoperatively,” he said.
	
	During wound closure and crease formation, the wounds can be closed with interrupted 6-0 or 7-0 nylon or Prolene sutures. In some cases, a crease may need to be created. Dr. Tovilla-Canales said he takes a small bite of the orbicularis muscles, a bite of the aponeurosis where it joins the tarsus and finally another bite of the orbicularis muscle in the upper incision.
	
	While UEB appears to be a simple procedure, complications can occur. This can include asymmetry, ptosis, lagophthalmos, ocular motility disorders, scarring, hematoma, retrobulbar hemorrhage, and lymphedema.
	
	“UEB is usually a safe and effective procedure,” Dr. Tovilla-Canales concluded. “Complications can be prevented by performing an adequate preoperative assessment, understanding the patient’s expectations, obtaining meticulous measurements for skin markings, and proper surgical technique.”

Dr. Tovilla-Canales has no financial interest in any aspect of this report.

Articles

No cookie-cutter procedure, UEB can improve patients’ visual fields by more than 25%

Pearls for upper eye lid blepharoplasty

Preventing and treating vitamin A deficiency is the first step in preventing systemic and ocular complications, including xerophthalmia.

, a form of dry eye that results from vitamin A deficiency, was recognized medically as far back as 1520 BC. A treatment was devised that involved cooking beef liver, and then squeezing the “juice” of the liver on the affected eyes, according to 

theorized that the juice from the liver trickled down through the lacrimal sac and was absorbed, entered the blood stream, and ultimately reached the back of the eye.
	
	Dr. Sommer, professor of ophthalmology,

, recounted his experience in 1978 in an Indonesian village during which he witnessed a similar ceremony performed on a child with nightblindness who was treated with goat’s liver and then given the liver to eat, which may be how the vitamin A entered the child’s circulation in the first place.
	
	


	
	A 19th-century treatment that was less humane advised keeping the affected person in a dark room for at least a month, which works temporarily because the retinal pigments have a chance to build up, Dr. Sommer explained. 

 is diagnosed currently by observing a patient’s response to various levels of light, a method that grew out of an observation in malnourished Confederate soldiers during the 

.
	
	The soldiers refused to take night watch because they could not see in the dark, which was confirmed by the lack of a pupillary response when a candle was waved in front of their eyes, Dr. Sommer noted. Another manifestation of xerophthalmia is the presence of Bitot’s spots on conjunctiva, which are comprised of keratin.
	
	“Vitamin A is necessary for development of normal, mucous-secreting conjunctival epithelium,” he explained.
	
	The spots usually develop temporally, but severe cases involve the entire conjunctiva. In the late 19th century, cod liver oil, which is rich in vitamins A and D, was determined to be an effective cure for night blindness and Bitot’s spots.


	
	Dr. Sommer described the case of a child who was vitamin A-deficient and had an unusual form of local necrosis.

“This manifestation often begins with a small ulcerative area that is hard to differentiate from an infection until the clinician realizes that nothing can be cultured from it and it is refractory to antibiotic treatment,” Dr. Sommer said.

 revealed the presence of liquefied corneal stroma over an intact epithelium.
	
	The 

n recommended treatment of the necrosis with water-miscible vitamin A, which was unavailable and required formulation. Dr. Sommer instead administered an oily preparation of vitamin A orally (it was known that it did not work when injected, as had long been taught) until the water-miscible formulation became available.
	
	The new formulation worked well when given intra-muscularly, but no better than the less expensive oily preparation given by mouth. Studies of locally necrotic corneal ulcers in children who died showed them to be strictly demarcated, absent of inflammatory cells, under an intact epithelium, and bordered by normal tissue.
	
	“It did not fit any of the suggestions we had about the mechanism by which sterile corneal melting would develop,” Dr. Sommer said.
	
	Because of the good results Dr. Sommer achieved with the cheap, available orally administered oily vitamin A, he compared it with the more expensive, less readily available water-miscible form administered intramuscularly.
	
	“The rates at which corneal healing occurred were very similar in the two groups,” he said. “We confirmed in 1980 that both the clinical and the biochemical responses were identical in the two groups.”
	
	At six to eight days after administration, the improved/cure rates were 94% and 97%. Early treatment of xerophthalmia is essential before the cornea is completely necrotic. The disease is associated with a mortality rate of about 25% despite hospital care.

Nutrition a priority for dry eye patients


	
	Keratomalacia is the most severe form of xerophthalmia. The association between the corneal deterioration and Bitot’s spot was not recognized until the early 1900s, about the same time as the discovery of vitamin A.
	
	This was a period when it was found that the so-called 

, i.e., fat, carbohydrates, and protein, were insufficient by themselves to sustain life, but, according to Dr. Sommer, life required “accessory factors,” as they were called by Hopkins, or “vital amines” by Funk, and fat-soluble A by McCollum and Davis.
	
	It was not until 1917, that McCollum reported, “We feel confident that these cases of xerophthalmia … should be looked upon as a deficiency disease not hitherto recognized in its true relationship to diet.”
	
	Dr. Sommer described a rat study in which pregnant rats were made vitamin A deficient and the pups were born severely deficient, to facilitate development of xerophthalmia and other manifestations of vitamin A deficiency. The deaths among the pups were charted. The results showed that xerophthalmia developed much later, after a number had died.
	
	This death rate was evident when Dr. Sommer and colleagues studied xerophthalmia in Indonesia and found that children with mild vitamin A deficiency, but with normal looking eyes, died at a third of the rate of those with nightblindness, which was one-sixth the rate of the children with 

.
	
	Further studies, and randomized trials, showed that by giving vitamin A by mouth twice a year to children in the developing world, would reduce childhood mortality by one-third.
	
	“This changed the paradigm,” he noted. “Instead of vitamin A deficiency equaling xerophthalmia, as the vitamin A status declines other systemic functions are seriously impacted.”
	
	The ocular manifestations, which had been considered the primary outcomes of vitamin A deficiency, develop relatively late. This recognition led to a program in 50 countries in which large-dose vitamin A capsules are distributed twice annually to all children younger than 5 years. This has been estimated to save about 350,000 lives annually.
	
	

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

Centuries of research show treating deficiencies can have dramatic impact

Focusing on xerophthalmia, vitamin A deficiency

-A trifocal diffractive lens (FineVision IOL, PhysIOL) reduces spectacle dependence after cataract  surgery and provides good patient satisfaction with uncorrected visual  capabilities for near, intermediate, and distance tasks. Sunil Shah, FRCS(Ed), FRCOphth, reported the results of a pilot study at the annual meeting of the American Society of Cataract and  Refractive Surgery.

This intraocular lens (IOL) is composed of two diffractive structures, according to Prof. Shah. The first diffractive  structure adds about 3.5 D for near vision and the second 1.75 D for intermediate vision.

Prof. Shah, who is a visiting professor, University of Aston, Birmingham, UK, and colleagues conducted a study that included 20 patients who underwent bilateral implantation of the IOL. Prof. Shah performed all of the surgical procedures. The primary goal of the study was to examine  visual outcomes following bilateral implantation of the IOL.

At 3 months postoperatively, the mean uncorrected postoperative monocular distance logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was 0.24 (20/20 = 0.0), the mean spherical equivalent 0.02, the mean logMAR best-corrected distance monocular (BCDVA) 0.12, and the mean logMAR binocular BCDVA 0.09, Prof. Shah said.

Following surgery, the patients were asked to complete a questionnaire to measure satisfaction. The questionnaire was specifically validated for use with  patients with accommodative and multifocal IOLs to assess their level of visual  independence. The responses to the quality of the VA could range from 0 to 4,  with 0 indicating complete satisfaction and 4 indicating completely unsatisfied.

“The  overall patient satisfaction at 3 months after implantation was 0.9 ± 0.9, a  result that is very similar to all the new multifocal IOLs being introduced,”  according to Prof. Shah.

Regarding  the defocus curve, the investigators found that the IOL maintained a moderate  level of VA 3 months postoperatively, which was better than that at all levels  of defocus, he explained.

“This  intraocular lens provides a clear area of intermediate VA not seen with other multifocal  IOLs,” he said.

“The  Fine Vision trifocal IOL works extremely well at three levels of VA and  provides good patient satisfaction with uncorrected vision,” Prof. Shah  concluded.

Prof. Shah has no financial interest in this  subject matter.

A trifocal diffractive intraocular lens (FineVision IOL, PhysIOL) reduces spectacle dependence after cataract surgery and provides patient satisfaction.

Trifocal diffractive intraocular lens reduces spectacle dependency


This article was reviewed by Sophia El Hamichi, MD

Retinoblastoma (RB) is the most frequently seen intraocular cancer in children, a complication of which is retinal detachment (RD). 

While the main focus of treatment is curing the cancer and preserving the eye, the visual function is important to the patient’s quality of life.

These cases are not without potential hurdles. The RDs can prove to be complex problems that are persistent, and therein lies the challenge to ophthalmologists, according to Sophia El Hamichi, MD, from Murray Ocular Oncology and Retina in Miami, Florida.


Retinal pathologies challenging to image with current technologies


El Hamichi and her colleagues conducted a retrospective study in which they reviewed and described persistent RDs in eyes with RBs, the etiologies, treatment attempts, and outcomes in this patient population between June 2012 and December 2019.

A review of the medical records identified 62 patients with RB during the study period. Persistence of RDs was defined as the presence of subretinal fluid after the patients had been treated for RB and achieved complete tumor regression. 

Of these patients, a RD developed in 42 (67%), of which 35 resolved successfully. 

The other 7 patients (5 boys, 2 girls) had a persistent RD; in these patients, the RB was bilateral in 3 patients and unilateral in 4. 

In all patients, the RB and RD presented simultaneously during the first ophthalmologic assessment. The mean age at diagnosis of RB was 11 months (range, 2 days-24 months). 


NR600 retinal prosthesis: Safe with promising visual results​ 

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The ages at diagnosis of RD ranged from 2 days to 24 months. All eyes had an advanced stage of RB, ie, state 5B in 8 eyes and stage 4 in 2 eyes.

Intraarterial chemotherapy was applied in 6 eyes of 5 patients and systemic chemotherapy in 3 patients; 1 patient was treated with intraarterial chemotherapy bilaterally and systemic chemotherapy. One patient underwent external beam radiation therapy and a periocular injection of carboplatin. Cryotherapy and intravitreal chemotherapy were not used on any patients.

The RDs were complex in all eyes. In 9 eyes, the detachment had exudative and tractional components. One eye had a pure tractional RD as the result of persistent fetal vasculature. The RDs were not repaired surgically in any eyes, El Hamichi said.

Following treatment, the tumors did not recur in any eyes. The eyes were anatomically stable. One patient had a globe phthisis in 1 eye, and another patient had a globe pre-phthisis; both patients had bilateral RBs and bilateral retinal detachments with poor visual outcomes.



Micropulse laser therapy a safe treatment for retinal disorders


In RB, exudative, rhegmatogenous, and tractional RDs can develop. The exudative type tends to occur when an exophytic RB is present subretinally and generally is associated with subretinal tumor seeding.

In these cases, when the tumor responses to chemotherapy, the RD was reported to resolve spontaneously.

Another study found that the first round of chemotherapy caused exudative RDs when eyes did not receive focal consolidation treatment, possibly because of excessive inflammation from chemoreduction or rapid tumor reduction.

Intra-arterial chemotherapy resolves 43% of total RDs and all partial RDs associated with RB.3 Exudative RDs have developed after intra-arterial chemotherapy that never resolved despite tumor regression.

Rhegmatogenous RDs probably develop as the result of focal retinal necrosis and retinal breaks that resulted from cryotherapy applied to the tumor area. The area around the tumor usually has an exudative RD present. 



Harnessing regeneration of retinal tissues: An option almost within reach



Another theory about rhegmatogenous RDs is that focal inflammation increases in response to cryotherapy in eyes with inflammation because of the tumor. 

Traction and breaks in weakened retinal zones result. These patients, most of whom undergo chemoreduction, are more susceptible to complications.

Some rhegmatogenous RDs have developed after intraarterial chemotherapy as a result of rapid tumor regression that leaves an atrophic retinal hole. Rhegmatogenous RDs seem to occur mostly in eyes with advanced disease with extensive endophytic tumors.



Intravitreally injected hRPCs improve vision in retinitis pigmentosa cases


The caveat in these eyes is that surgery in the presence of active RB carries a high risk of tumor metastasis.

Pars plana vitrectomy can be an option in cases of RD of more than 1 mechanism in an attempt to restore the retinal anatomy and possibly vision. 

However, the investigators pointed out that the risk of tumor dissemination outweighs the benefit of repairing the RD. 

The investigators recommended that surgery not be performed until 2 years after the patient underwent their last treatment for RB. If the RB is not controlled, enucleation is mandatory.

Based on the study findings, the investigators concluded, “the development of RD can be challenging in cases of RB, especially when it has a complex configuration leading to persistence of the RD. These RDs are difficult to treat, and the visual outcomes can be compromised. Vitrectomy should not be performed until the patient is free of RB for 2 years to avoid spreading the tumor and metastatic disease. This waiting period affects the surgical results and even calls into question its necessity.” 



El Hamichi has no financial interest in this subject matter.

1. Shields JA, Shields CL. Management of retinoblastoma. In: Shields JA, Shields CL, eds. 

Intraocular Tumors: An Atlas and Textbook.

 Lippincott Williams Wilkins; 2008:334-351.

2. Elaraoud I, Ch’ng S, Karl D, Kalogeropoulos D, Chavan R, Sharma A. Management of retinal detachment in retinoblastoma with globe conserving treatment. 

. 2018;31(1):43-48. doi:10.1016/j.joco.2018.09.002

3. Shields CL, Kaliki S, Shah SU, Bianciotto CG, Jabbour P, Shields JA. Effect of intraarterial chemotherapy on retinoblastoma-induced retinal detachment. 

. 2012;32(4):799-804. doi:10.1097/IAE.0b013e31823d8e1e

Watchful waiting may prove to be beneficial in complicated cases

Persistent retinal detachment connected to retinoblastoma

This article was reviewed by Scott E. LaBorwit, MD



Practitioners can decrease the treatment burden for patients through the use of available generic and low-cost intraoperative medications that negate the need for patients to purchase medications postoperatively, according to Scott E. LaBorwit, MD.

For example, practitioners can compound antibiotics and steroids and administer them perioperatively via a transzonular or a pars plana approach; however, 

surgeons might not be comfortable with such a procedure. 

Another costly option is steroids that can be deposited in the lacrimal system or under the iris.


Dropless, hands-free regimen key for patients


LaBorwit and Robert Stutman, OD, MBA, conducted a retrospective chart review to identify safe generic or low-cost medications for use at surgery to eliminate patient expenses after surgery.

The sample size was 5400 patients who underwent 

by 1 surgeon from July 2016 to January 2020. The study’s end point was the absence of the need for patient medication purchases after 

The study’s hypothesis was that use of perioperative antibiotic drops, povidone-iodine 5% during the surgical prep, anterior chamber generic moxifloxacin, and sub-Tenon triamcinolone will eliminate the need for preoperative or postoperative drops.

The investigators evaluated the safety outcomes, which included the incidence rates of infection, IOP elevations resulting from steroids, rebound iritis, and cystoid macular edema, LaBorwit recounted.

They used generic moxifloxacin 1 mg/mL from a commercially available bottle (cost, $47.50 per bottle) with 0.3 cc instilled into the anterior chamber; the moxifloxacin was diluted with balanced saline solution in a 1:4 ratio. The cost per patient of this approach was $1.06, LaBorwit noted. 

For the steroid component of the treatment, the investigators injected 0.3 cc of triamcinolone 7 mm posterior to the limbus into the superonasal sub-Tenon space; the dose was later decreased to 0.1 cc. The triamcinolone cost $43 per vial and $1.07 per patient.

Topical moxifloxacin: Best choice before cataract surgery?


No intraocular complications occurred as a result of the medication placement. Endophthalmitis did not develop in any cases. Three corneal ulcers developed that resolved with topical and anterior chamber treatment, LaBorwit explained.

The study results showed steroid-induced elevations in the IOP in 102 patients (1.9%), and these were treated with topical antiglaucoma medications. 

With reduction of the dose from 0.3 to 0.1 cc, the incidence rate of elevated IOP decreased to 0.67%. Nine (0.17%) patients had persistently elevated IOPs that exceeded 30 days postoperatively.

Predictable, branded steroids offer control over surgery

Cystoid macular edema developed in 1.5% of patients for an average of 35 days. All resolved with drops over time. 

Rebound iritis occurred in about 5% of patients, which increased to 6.67% when the steroid volume was decreased, LaBorwit noted.

“The results indicated that generic and low-cost intraoperative medications use is safe and effective and eliminates the need for patients to buy drops postoperatively. The total cost to the surgical center was less than $3 per patient,” LaBorwit concluded.

LaBorwit has no financial interest in this subject matter. Dr LaBorwit is an assistant professor at Wilmer Eye Institute, The Johns Hopkins Hospital, Baltimore, Maryland. Robert Stutman, OD, MBA, is an optometrist in Towson, Maryland.

Options can reduce the treatment burden for patients, leading to improved outcomes


Perioperative medications can eliminate postoperative drops after cataract surgery

Great inventions start with an idea, but only a small fraction moves past that phase through increasingly complicated, work-intensive developmental stages.

Leaders in the field guided investigators through the route their ideas must take to reach fruition. Malik Kahook, MD, professor of ophthalmology, University of Colorado, and Adrienne Graves, PhD, co-founder and co-chair of Glaucoma 360, moderated this discussion.

Considerations when attempting to “grow” an idea into a viable product are the risks involved—emotional, financial, and reputational. 

“These factors seem theoretical until they become real, as people are judging if your approach is sound,” said John Berdahl, MD, who is in private practice at Vance Thompson Vision, Sioux Falls, South Dakota.

The next step is determining if the idea is good (i.e., interesting and important) and can satisfy a marketable need. This stage must be coupled with a high level of motivation to pursue that idea and accomplish the level of work needed to bring it to realization. Finding mentors, performing proof-of-concept science, and being honest with all involved individuals about whether the idea will take off are also mandatory steps.

Importantly, the idea must be legally protected with a patent. Entrepreneurs must protect a space to prevent others from developing something similar.

Berdahl also offered a practical tip: develop the intellectual property before starting the company and then license the property to the company for a royalty. Physicians must also learn about how venture deals are structured, executing a business, and staying focused.

Forge pathways through the FDA and reimbursements. Berdahl advised engaging early with the FDA (which provides useful information about achieving approval) and payers to determine what can be reimbursed. Team building is the final and perhaps most vulnerable step to assemble a group of people who are dedicated to making the idea a reality.

“The next step after developing a medical prototype is raising capital,” said Reza Zadno, PhD, CEO of Glaukos. This is easier said than done for novice entrepreneurs. Raising capital also presents questions about who benefits from the product, the patient with better outcomes, the provider with shorter surgical times and better economics, or the payers?

“The most exciting projects for potential investors are those that satisfy everyone—generally high-risk, high-benefit projects,” Zando said. “However, they are also more difficult. A clear path is needed because the patients, provider, payer, and the costs of goods are generally unclear.”

The parties involved evoke myriad questions. For regulators: the FDA history with similar products, regulatory pathways, and is the product paid for by the patient or reimbursed? Have investors lost money with similar products? Are providers interested in new technology?

In some cases, a prototype is not always necessary.

Experience is key to selling the project—with an experienced founder who can define a clear pathway and risk for investors and with experienced capitalists who will ultimately invest in the project.

Every step in the process of developing a new treatment involves establishing and ensuring continuous funding, according to Eugene de Juan Jr, MD, vice chairman of ForSight Labs.

The key to keeping venture capitalists interested in a project is by reducing risk, he noted.

“Entrepreneurs must design, think, [create a] prototype, and test continuously to show that whatever they have is working,” he said.

To ensure the money flow, developers must ask if the product solves a clinical need.

“Human experience is what drives the needle, rather than in vitro and animal models,” de Juan emphasized.

Another consideration is the form. He continued, “Is it attractive? Do patients, doctors, and payers like it?”

Some thoughts for ophthalmologists to live by: Costs increase immensely with decreasing risk as the clinical programs progress. The risks of not progressing through the stage of development increase with each step; failing early can be absorbed by large, not small, companies.

There is a 50% chance of a drug getting through a phase 2 trial. Overall, the success rate from a drug to a clinical approved outcome is about 1 in 100.

The key to not failing late is not to start if failure is in the cards.

The Center for Drug Evaluation and Research ensures that safe and effective products are available for the American public. 

Our goal is to try to approve products that are safe and efficacious,” said Wiley Chambers, MD, deputy director of the Division of Transplant and Ophthalmology Products in the Center for Drug Evaluation and Research of the FDA.

When a product is involved in the approval process, Chambers advises applicants not to do something that they believe the FDA wants them to do when the company and the FDA do not think it is necessary.

The product being tested must have a vehicle that is an acceptable control.

The noninferiority margin is based on multiple previous drug trials. The 95% confidence interval that shows the test product produces the same result as the other products most of the time within 1 mm Hg indicates that within that margin, the drugs are the same, he explained.

In the United States, the generic solutions of timolol, bimatoprost, latanoprost, and travoprost have the same active and inactive ingredients in the same concentrations and these can be used in clinical trials.

The FDA requires comparisons of the peak and trough times of the drug tested and the control, that the measurements are done 2 weeks after treatment onset to be certain of the drug’s effect, and measurements are performed at 12 weeks because drugs that work then continue to be efficacious after that time. The FDA also wants drugs to be studied bilaterally as long as the eyes are within 5 mm Hg. “There are reasons behind everything the FDA asks for,” he said. “If you don’t know the reason, please ask.”

If considering a start-up, Thomas A. Mitro, president and chief operating officer of Aerie Pharmaceuticals Inc., advised hiring the best, most experienced people, who are not necessarily the most affordable, to lead the company through start-up turmoil.

In line with that, he also advised that they be paid well and not in stock options, before another company scoops them up.

Virtual start-up companies (and departments within those companies)—although very attractive—are difficult to build and establish the company culture and repertoire among employees scattered across the United States and globally.

To combat the negative aspects of having a company with multiple sites worldwide, Aerie Pharmaceuticals brings all employees together at 1 location for an annual meeting. The company also encourages immediate decision making by employees.

“Quick start-ups are encouraged and in like manner, fail as quickly as possible. Long exits waste time and money,” Mitro said.

He advised companies not to fall prey to failures by other companies in the industry that are attempting similar start-ups.

Finally, Mitro advised building relationships, not enemies; other companies should be considered competitors who are treated with respect.

Researchers must weigh emotional, financial, and reputational considerations