Thursday, December 31, 2015

Stem Cells in Ophthalmology Update 24: Current Tables Now Online

My current stem cell/cell therapy tables are now online for anyone interested to access. Here is a brief description of what is available and how to access them:

Stem Cell/Cell Therapy Companies/Institutions Active in Ophthalmology

A list of forty-two companies and institutions working with stem cells/cell therapies for ophthalmic applications. The table lists collaborators, the cell type being used, and the applications for which the cells will be used.

Stem Cell/Cell Therapy in Ophthalmology by Application

A list of eighteen ophthalmic applications being studied and/or in clinical trials. The table includes the companies/institutions involved, the clinical trial status, and an active link for the clinical trial for those listed. (sixty-one active and completed clinical trials are shown.)

Stem Cell/Cell Therapy in Ophthalmology -- Ongoing & Completed Clinical Trial Details

A list of the the eighteen ophthalmic applications and the sixty-one clinical trials showing the number of patients to be studied in each trial and the number studied to date (that I am aware of). Active links are provided for each ongoing or completed trial.


Updated December 31, 2015. 

Tuesday, December 01, 2015

Articles Published in Ophthalmic Journals in 2015

In addition to the several updates posted on this blog in 2015 (see previous posting), I have prepared four articles that have appeared in ophthalmic journals this year.

Here is a brief summary of the four articles, including links to the online versions:

Regenerating the Retina - February 2015

This article, published in the February 2015 issue of The Ophthalmologist, describes the use of stem cell-derived retinal progenitor cells (RPCs), that are being investigated for reviving/repairing/rejuvenating damaged photoreceptors to bring back sight to those who have lost it due to a retinal degenerative disease, including choroideremeia (CHM), retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA) and Stargardt’s disease (Stargardt Macular Dystrophy - SMD). It discusses the four companies that are conducting clinical research, as well as the work underway at several university and institutional laboratories.

To read the complete write up, please use the following link:

Update: Since the article appeared, two of the companies discussed, jCyte and ReNeuron have either begun a clinical trial (jCyte), or announced the start of one (ReNeuron).

With the likelihood of a gene therapy and/or a stem cell treatment for retinal diseases to be approved for marketing within the next two to three years, it is time for the ophthalmic community – the suppliers, practitioners, patients and payers –  to start thinking about how much these regenerative medicine treatments are likely to cost, and how patients and the healthcare system will pay for them..

In The Economics of Gene Therapy, appearing in the May 2015 issue of The Ophthalmologist, I propose a pricing model for Regenerative Medicine in Ophthalmology, based on the population of patients to be treated, and suggest that an annuity program model, based on performance and duration of efficacy, could be used to pay for it.

Let the dialogue begin.

To read all about it, please follow this link:

An update of the latest clinical information in the use of gene therapy in treating several retinal diseases, including Leber’s Congenital Amaurosis (LCA); the wet form of Age-Related Macular Degeneration (wet-AMD); Choroideremia (CHM); Stargardt’s Macular Dystrophy (SMD); Retinitis Pigmentosa (RP); and Ushers Syndrome (US). Included is the proposed model of pricing for some gene therapy treatments, based on the population of patients likely to be treated.

To read the full article, published in the October issue of Retinal Physician, please follow this link:

Optogenetics is the introduction of protein-based, light-activated chemicals into still functional retinal cells in the vision chain, that upon activation, send electrical signals along the optic nerve to the brain, providing rudimentary vision, that was lost with the death or damage of the photoreceptors.

This report, The Optogenetics Option, describes the efforts of four companies and ten universities, using either gene therapy, or other means, to deliver light-activatable proteins or chemicals (photoswitches) to still functioning cells within the retina (ganglion and/or bipolar cells) or, in some cases, the use of light activatable implants, that will deliver light signals to the brain to provide some rudimentary vision when the photoreceptors, that normally provide that function, cannot.

To read the article, published in the November issue of The Ophthalmologist, please follow this link:

Blog Articles Published in 2015

2015 was another busy year in writing about new developments in treating retinal diseases. During the year, I published seven blog entries (and another four published articles - to be indexed separately). Here are the highlights of the blog writeups:

Since I last wrote about Iluvien, Alimera Sciences and pSivida have announced additional marketing approvals for its use in treating chronic DME. The product is now approved for use in fourteen countries, including the U.S. In addition, pSivida is about to begin a Phase III study of its Medidur device for the treatment of uveitis, which should lead to a fast-track to approval.

But the real reason for this update was the recently published story about how an eye doctor reached out to Paul Ashton, CEO of pSivida, to package an old HIV anti-viral, ganciclovir, in his drug delivery system, to save the sight of a person undergoing chemotherapy for leukemia, who also needed a bone marrow transplant. The chemo and radiation treatment for the bone marrow transplant weakened his immune system, preventing control of his cytomegalovirus condition that began attacking his retina. Instead of painful weekly anti-viral injections, the doctor sought to use Paul’s drug delivery system to systemically treat the virus in the eye.

To read the whole story and the results, and for the latest information about Iluvien, please follow this link:

With the presentation of the three-year safety results of the INTREPID study (at EURETINA), to evaluate the safety and efficacy of the Oraya Iray Therapy in conjunction with as-needed anti-VEGF injections for wet AMD, and the recent collaboration agreement with Carl Zeiss Meditec, Oraya Therapeutics is well on its way in implementing its growth strategy in commercializing Oraya Therapy in Europe and, some day, in the U.S.

The company now has nine centers providing therapeutic treatment in Europe; four centers in the UK, one in Switzerland, and four in Germany.

To read more about this combination treatment to reduce the number of anti-VEGF treatments needed to control wet AMD, and the collaboration agreement with Carl Zeiss Meditec, please see:

Avalanche Biotechnologies in Menlo Park and the University of Washington in Seattle announced a licensing agreement to develop the first gene therapy treatment for treating color blindness. The deal brings together a gene therapy technique developed by Avalanche with the expertise of vision researchers at the University of Washington.

In addition, Avalanche will incorporate research licensed from UCal Berkeley to deliver the gene therapy treatment non-surgically via an  injection into the vitreous, rather than into the retina.

To read more, please follow this link:

As Crystal Gayle sang in her smash hit, `Don't It Make My Brown Eyes Blue', now (soon) you will be able to permanently change your brown eyes to blue. A California company has come up with a laser procedure that will safely accomplish this in about 30 seconds per eye. Human clinical testing is underway and the company, Strōma Medical, hopes to have the procedure on the market (outside of the U.S. first) in less than two years, once the clinical trials are completed.

To read the rest of the story, please follow this link:

My article about the use of lasers to treat floaters, written five year ago, remains the most widely read piece on my blog. I frequently am asked if I have updated the list of doctors who now use lasers to treat floaters - in addition to the three I profiled in my U.S. writeup (Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis) and the six doctors in the UK/Europe piece (Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis in the UK and Europe).

I took notice when Ellex Medical announced a new YAG laser specifically for treating floaters in the fall of 2012, and about six months ago, I decided to request a list of doctors who have obtained the laser, and were now treating patients’ floaters. Better than a list, Ellex decided, to respond to my request, by building an app to locate doctors using their laser and put it on their website. That app is now active and is applicable to doctors worldwide using the new Ultra Q Reflex YAG laser to treat floaters. As of June 30th, there are 58 physicians listed worldwide using this laser.

To read more about the laser and use the app, see my update:

Some insight into the Spark Therapeutics Phase III clinical trial results and longevity data. In this report, the company’s principal investigator, Dr. Stephen Russell presented highlights of the initial findings in this important Phase III clinical trial, that could lead to the first gene therapy approval in the United States.

Basically, it was found that the injection of SPK-RPR65 did lead to increased functional vision for the treated patients, compared to the control subjects - and the effect appears to last for over three years, based on the original patients treated in the Phase I study.

Is this the “forever fix”, or a step along the way? To read the full story, please follow this link:

Three German ophthalmological groups provided guidance for German ophthalmologists to better identify those patients with wet AMD that might benefit from the use of the Iray Stereotactic Radiotherapy System as an adjuctive treatment to the use of anti-VEGFs in the treatment of neovascular macular degeneration, based on studies conducted by the company to date.

To read the full story, please follow this link:

Tuesday, October 20, 2015

Oraya IRay Update 4: Oraya Therapeutics Receives Guidance for Use in Germany

When I last updated the progress of Oraya Therapeutics, in January of this year (Oraya IRay Update 3: Oraya Now Operating at Nine European Centers and Partnership with Carl Zeiss Meditec), I noted the collaboration agreement between Oraya and Carl Zeiss Meditec to provide funding to Oraya over a period of up to two years for the implementation of Oraya's growth strategy, and I reported on the three-year INTREPID safety results, presented the previous September. Here now is the latest information on the progress of the company to bring this adjunctive treatment for the wet form of AMD to the professions.

The German Ophthalmological Society, the Retina Society and the Professional Association of German Ophthalmologists (DOG) have issued a joint opinion on the adjunctive use of radiotherapy with Oraya Therapeutics' IRay Stereotactic Radiotherapy System for wet AMD. Their opinion makes it possible for ophthalmologists throughout Germany to identify patients that can benefit from Oraya Therapy in conjunction with anti-VEGF treatment.

Oraya Therapy is currently commercially available at eleven sites in Europe, with more than 550 patients treated to date with Oraya Therapy in three European countries - Germany, Switzerland and the United Kingdom.

According to the opinion, which takes the study data published to date into account, adjunctive stereotactic radiotherapy of neovascular AMD with the IRay system can be considered on an individual basis. Some of the parameters that ophthalmologists should consider include:

●    If symptoms of choroidal neovascularization (CNV) activity such as intra-retinal fluid of bleeding are present, corresponding to a recommendation of VEGF inhibitors;
●    If the ongoing anti-VEGF therapy has taken place over a period of at least six months, thus ruling out undertreatment; and,
●    If despite intensive injection therapy, no change in the activity state of the CNV is achieved and there is no reasonable expectation of a decrease of the required high frequency of retreatment for the future.

"The joint opinion now provides guidance for ophthalmologists throughout Germany to identify those patients who can benefit from Oraya Therapy for wet AMD. There is a large patient population that does not respond well to anti-VEGF monotherapy, and our aim is to offer these patients in Germany an additional option to maintain their vision and also decrease the burden of frequent injections," said Oraya Therapeutics CEO Jim Taylor. "We are well positioned with our IRay system at major university eye clinics in Germany, and will continue to expand our presence to make the therapy available to the patients who qualify and elect to pursue this alternative."

The full opinion, titled "Stellungnahme von DOG, RG und BVA zur Strahlentherapie bei neovaskulärer altersabhängiger Makuladegeneration" is accessible within the German Ophthalmological Society website at:

The IRay Radiotherapy system is a CE marked medical device. In the U.S., the IRay system is an investigational device and is not yet available for sale.

For any of you reading this for the first time, please refer to my original full report describing the IRay system: Oraya IRay In-office Stereotactic X-ray Treatment for AMD: A First Report, written in January 2009.

Wednesday, October 14, 2015

Gene Therapy in Ophthalmology Update 22: First Spark Therapeutic Phase III Clinical Trial Results and Phase I Longevity Data

My article updating the latest information on the status of gene therapy clinical trials, What’s New in Gene Therapy for Ophthalmology? was published in the October issue of Retinal Physician. The final draft was submitted just prior to this important news from Spark Therapeutics providing information about their Phase III clinical trial results.

Principal Investigator Stephen R. Russell, MD, of the Stephen A. Wynn Institute for Vision Research at the University of Iowa, presented Phase III data highlighting the rate, breadth and magnitude of changes following administration of SPK-RPE65 to patients with Leber’s Congenital Amaurosis (LCA), at the Retina Society Meeting held in Paris on October 10th.

In addition, Dr. Russell presented data on the three-year durability of improvements in the same measures of functional vision and light sensitivity in a cohort of subjects from the earlier Phase I trial.

This presentation built on top-line results of a randomized controlled multi-center Phase III trial previously announced by Spark on October 5, which demonstrated a highly statistically significant improvement in the intervention group compared to the control group in the primary endpoint and two of three secondary endpoints.

Significant Improvements and Strong Parallels in Mobility and Light Sensitivity Testing

Data presented highlighted a mean improvement in the functional vision of intervention subjects (n=20) of 1.9 specified lux levels, compared with an improvement of 0.2 specified lux levels in control subjects (n=9) as measured by the change in bilateral mobility testing (MT) between baseline and one year in the modified intent-to-treat (mITT) population. The mITT population (n=29) includes all subjects that received SPK-RPR65, and only those who continued beyond the baseline study visit. Two subjects in the intent-to-treat (ITT) population (n=31) that were randomized but never received SPK-RPE65 are excluded from this efficacy analysis population. Thirteen of the 20 subjects receiving SPK-RPE65 were able to pass the MT at one lux at year one, demonstrating maximum improvement measurable on the MT score. None of the nine control subjects followed was able to pass MT at one lux at year one.

In a corresponding finding in the first secondary efficacy endpoint, full-field light sensitivity threshold testing (FST*) for white light, intervention subjects demonstrated a highly statistically significant mean improvement of -2.06 log10 (candela second/m2) compared with decline of 0.04 log10 (candela second/m2) among control subjects (all analyses in mITT population).

(*FST is a full-field light sensitivity threshold test. As RPE65-mediated retinal dystrophies primarily affect rod photoreceptors first, night blindness and loss of peripheral vision are typically the presenting symptoms; central vision may be relatively spared initially. Thus FST was the first hierarchically-arranged secondary as opposed, for example, to visual acuity. It is more reflective of the underlying pathophysiology of the disease.)

Dr. Russell presented additional top-line analyses from the pivotal Phase III trial showing the rapid and sustained impact of SPK-RPE65 throughout the entire one-year study period. Significant differences emerged in both MT and FST by the first study visit, at 30 days. These effects were reproduced consistently at each subsequent study visit (at days 90, 180 and one year).

Dr. Russell said, "It's exciting to see a consistency of improvement between the functional vision and visual function. The parallel effect seen in the prompt response in both the primary and first secondary endpoints highlights a critically important finding from the trial: that functional improvements measured through the mobility test change score correspond closely with the physiologic impact seen through FST."

Figure 1: Phase III Trial of SPK-RPE65: MT and FST Over Time (mITT)

In addition, Dr. Russell presented data on the durability of effect after three years as measured by MT and FST in a cohort of subjects that participated in the Phase 1 open-label study, and would likely have met the eligibility criteria for the Phase 3 trial. All of these subjects continue to experience a durable improvement over three years from the time of administration to the contralateral, or second eye, with observation ongoing. These subjects received the same dose and volume of SPK-RPE65 that was used in the pivotal Phase 3 trial. The figures below reflect data from all subjects available for follow-up at each time point reported. Spark and the clinical investigators continue to follow study participants to evaluate the durability of response, and will provide further updates in the future through a series of peer-reviewed presentations and publications.

"We are pleased to provide these additional informative data, the totality of which highlight the rapid, sustained and durable effect associated with SPK-RPE65 across multiple functional and physiological parameters, at time points ranging from 30 days to three years," said Jeffrey D. Marrazzo, co-founder and chief executive officer of Spark. "We will continue to analyze the data from our groundbreaking pivotal Phase 3 trial in order to further elucidate the potential positive, meaningful impact that SPK-RPE65 can have on the lives of patients with RPE65-mediated blinding conditions."

Figure 2: Phase 1 Trial of SPK-RPE65: Durability of MT and FST Over Time

Pivotal, Phase 3 Trial Overview

The pivotal Phase 3 trial of SPK-RPE65 is the first successful randomized, controlled Phase 3 trial ever completed in gene therapy for a genetic disease. The multicenter trial randomized 31 subjects with confirmed RPE65 (LCA) gene mutations. The ITT population included 21 subjects in the intervention group and 10 in the control group.

For the primary endpoint, subjects were evaluated at multiple time points over the course of one year for their performance in navigating a mobility course under a variety of specified light levels ranging from one lux (equivalent to a moonless summer night) to 400 lux (a brightly lit office) using the bilateral testing condition. Each attempt was recorded, and the videos were sent to independent, centralized, masked graders to assign a pass/fail score based on speed and accuracy with which the subjects navigated the course.

In addition to the primary endpoint, the statistical analysis plan included three secondary endpoints tested statistically in the following hierarchical order:

●    FST (white light), which reflects underlying physiological function by measuring light sensitivity of the entire visual field.
●    Change in MT score for the assigned first eye, which compares the MT performance between baseline and year one for the first eye injected for the intervention group and, for the control group during the control year, the first eye injected after they crossed over.

●    Visual acuity (VA) testing, which measures changes in central vision by assessing the ability of the subject to read a standard eye chart.

A summary of top-line efficacy results follows:

Primary outcome (ITT)    
MT change score, bilateral      p = 0.001

Secondary outcomes (ITT)    
FST, averaged over both eyes               p < 0.001
MT change score, first injected eye      p = 0.001
VA, averaged over both eyes                p = 0.17

So What Does All This Mean?

In a story about the trial results published by Bloomberg Business News, the reporters commented, “A gene therapy maker showed this week it could make blind children and adults see. But the big question left is how long the effect will last.”

“Much depends on the answer, including how much the company can charge for the drug -- a price tag some say could be more than $1 million a patient.”

The company has shown the effect has lasted for as long as three years without degradation of vision in some patients, providing back functional vision to those nearly blind children treated in the initial clinical trial.

According to Dr. Russell, the principal investigator, "Investors will look at the data and are going to go, `Wow this is the best data we've seen, not just in the eye, but on gene therapy, period' and they're right,"

Yet he cautioned that more information is needed before the drug can be considered a cure. While it produces a missing enzyme needed to sense light, it can't restore light-sensing cells that have already died off due to this progressive disease. In the initial study results, released on October 5th, one standard measure of vision, visual acuity, didn't improve by a statistically significant amount. (But, functional vision did!)

Spark also hasn't finalized and published data on individual patients, and it's possible that some responded better than others. “Age in particular may be a factor in how much a patient can improve,” said Dr. Russell. The company said in its statement that no serious adverse events have been seen so far in the trial.

So, the question remains, is this the “forever fix”, as author Riki Lewis has written in her book on gene therapy, or something less? Time will tell. But this is certainly an important step forward for the treatment of an inherited retinal disease.


1.  What’s New in Gene Therapy for Ophthalmology?, Irv Arons, Retinal Physician, October 2015.

Stephen R. Russell MD, Retina Society Meeting, Paris, Stephen R. Russell MD, October 10, 2015.

5. 'Holy Grail' Seen as Gene Drug for Blind Produces Lasting Effect, Caroline Chen & Robert Langreth, Bloomberg Business News, October 10, 2015.

Tuesday, September 01, 2015

Gene Therapy in Ophthalmology Update 16: Current Tables Now Online

My current gene therapy tables are now online for anyone interested to access. Here is a brief description of what is available and how to access them:

Gene Therapy

Gene Therapy Companies/Institutions Active in Ophthalmology

The table lists more than forty-two companies and institutions actively pursuing gene therapy solutions to ophthalmic diseases. The table shows the delivery viral platform, the gene type being used (where known), the application, and clinical status.

Gene Therapy in Ophthalmology by Application
This table lists the twenty-two ophthalmic indications, the company/institutions involved, the clinical status, and the clinical trial number. (Thirty active clinical trials are listed, with live links.)

Gene Therapy in Ophthalmology -- Ongoing Clinical Trial Details
This table lists the thirty active and completed clinical trials, the number of patients to be treated and the number of patients treated to date (that I'm aware of).

Updated February 14, 2016

Tuesday, June 30, 2015

Using Lasers to Treat Vitreous Floaters: An Update

Since my first article on the use of a YAG laser to treat floaters (Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis) appeared in this space in August 2010, it has become the most popular/read write-up that I have posted. About 10% of all visitors to my blog come to read that article - and I’ve had over 215,000 unique visitors. One of the most frequent questions I get asked is, is there anyone close to where I live that does the procedure? Since I haven’t kept track of who besides the three doctors I featured in that first write-up are now doing the procedure, and since Ellex Medical (Ellex) now produces and markets a specialized laser (the Ultra Q Reflex) specifically to treat floaters, I decided it was time for this update.

As described by Ellex, upon release of their new laser in the Fall of 2012, here are its features:

"Featuring Ellex's proprietary Reflex light delivery system, our ophthalmologist customers can  use the Ultra Q Reflex YAG laser to treat floaters in a medically-reimbursable procedure, known as YAG laser vitreolysis," according to Ellex CEO Tom Spurling.

While there are several YAG lasers on the market, none until now were designed specifically for the treatment of floaters.

"The Ultra Q Reflex is optimized for performing YAG laser treatments both in the anterior segment and posterior segment - making it ideal for the all conventional YAG laser treatments such as capsulotomy and iridotomy, as well as YAG laser vitreolysis for the treatment of floaters," added Mr. Spurling.

Ultra Q Reflex for Nd:YAG Laser Vitreolysis

Floaters (vitreous strands) are small bundles of collagen fibers located in the eye's vitreous, which cast visual shadows that impede quality of vision. Often considered benign, they are a result of degenerative vitreous syndrome (DVS; the natural breakdown and clumping of collagen in the vitreous) and posterior vitreous detachment (PVD; the age-related separation of the vitreous from the retina).

To date, surgical removal of the vitreous (vitrectomy) has been the standard approach to the treatment of floaters. Highly invasive, the procedure carries a significant risk of complications, such as infection, retinal detachment, macular edema, anterior vitreous detachment and residual floaters.

The proprietary slit lamp illumination tower design of the Ultra Q Reflex converges the operator's vision, the target illumination, and the treatment beam onto the same optical path, and focuses them onto the same optical plane as the treatment beam. This minimizes the potential for focusing errors and the risk of damage to the natural lens or the retina -- making the Ultra Q Reflex ideal for the treatment of floaters. In contrast, conventional YAG lasers offer a limited view of the vitreous, which can make it difficult to visualize vitreous strands and opacities.

I contacted Ellex Laser management and requested a list of the U.S. doctors who have purchased this laser and who now use it to treat their patient’s vitreous strands/floaters. The company, in response to my request,  has set up an application on its website, called “Find a Physician”.

By entering your location, a map will appear which will locate doctors near you that have access to this specialized laser and use it to treat vitreous floaters by performing laser vitreolysis. The link to the app is:

PS: The app works worldwide!

(As of June 30th, there are 58 physicians across North America, Australia, Asia, and parts of Europe who have decided to be referenced in the physician finder.)

Good luck to all.


Wednesday, April 08, 2015

A Laser Process for Changing Brown Eyes Blue

`Don't It Make My Brown Eyes Blue' was a smash hit song(1) for Crystal Gale in 1977. But it has been a wish for many a young girl with brown eyes (and even some older ones and perhaps some men) ever since. Over the years it has been possible to turn your brown eyes blue using contact lenses, first lightly tinted ones, which really didn’t do much for dark brown eyes, and later opaque tinted lenses, which would cover brown pigmented eyes and really turn them blue (or green or even other colors), although they created an opaque light eye, which does not exist in nature and thus looks contrived. There are even a couple of surgical procedures that can transform the iris, or enhance/darken the edge, but the question of safety quickly arises with any surgical procedure.

So, a week ago, when my wife told me what she had just seen that there was a laser process to turn brown eyes blue, on The View, I replied, “No way”. You see, I was a consultant to the medical laser industry, involved in the use of lasers in both ophthalmology and cosmetic surgery, for over twenty years and had never heard of lasers used in this way. Just to be sure, I Googled it, and much to my surprise, yes, a company, Strōma Medical Corporation, in Laguna Beach California, is developing a permanent, non-surgical laser procedure that will turn brown eyes blue!

I found an article written for Ophthalmology Business(2) that explained how they were doing it. It also listed a couple of well-known ophthalmologists – Perry Binder and Marguerite McDonald, who I know on a personal basis – that are involved with the company, on their Medical Advisory Board, thus assuring me that this business was legitimate. I got in touch with my ophthalmologist friends and they put me in touch with the Chairman and Chief Scientific Officer of the company, Dr. Gregg Homer, to learn more.

What I have learned is that the company has developed a unique, low intensity, highly specialized laser and diagnostic aiming system (with computerized iris mapping and tracking), that targets the brown pigment on the front surface of the iris, removing some or all of that pigment, thereby revealing the natural blue eye lying below.  (The blue in an eye is actually the result of the scattering of white light entering the iris, by tiny grey collagen fibers called “stroma”, and the reflection of the shorter blue light, similar to the light scattering of sunlight by atmospheric molecules that makes the sky appear to be blue.)

A half treated eye (for illustration purposes).

As explained by Dr. McDonald in the Ophthalmology Business article, describing how the procedure works, “This is a Q-switched neodynmium YAG laser, which produces a very highly discriminatory photo-absorbed frequency. The laser fires a series of small, computer-guided pulses across the iris, to photo-disrupt the stromal melanocytes (the brown pigment). Because of the photo-absorption properties of this laser, the energy passes through the clear cornea and it very selectively hits the brown melanocytes, leaving the cornea and the posterior iris stroma totally undisturbed. The photo-disrupted melanocytes release cytokine protein molecules into the anterior chamber and the cytokine signal recruits macrophages...that engulf and digest the photo-disturbed melanocytes as cellular debris.”

To put it in simpler terms, the laser beam “breaks up” the brown pigment in the front part of the iris into much smaller particles, similar to the way lasers are used to remove tattoos, by a process known as “selective photothermolysis”(3). This phenomenon, invented by Drs. John Parrish and Rox Anderson of the Wellman Laboratories of Photomedicine at Massachusetts General Hospital, uses the principle of delivering pulsed laser energy to a selected chromaphore within the target tissue, without damaging surrounding tissue.

Illustration of the iris in cross section, showing the anterior border layer, which is the target of the Strōma Medical process.

The smaller particles are then digested by the macrophages formed and eliminated from the iris and from the anterior chamber via the normal liquid outflow channels in the eye.

The Story Behind the Story

According to Dr. Homer, he became interested in the concept of changing eye color in the late 1990s, discovering a paper in the literature on iris pigmentation by RC Eagle Jr.(4) “I finally found that paper, which wasn’t available digitally, and I thought, ‘Now that we’ve done so much work with lasers on dermal pigment, it should be fairly easy to remove that iris pigment safely, which should, in turn, reveal a blue eye.” He went on, “Around 2001, I personally funded a small study at Cedars-Sinai Eye Institute in Los Angeles. We took brown-eyed rabbits and proved the concept, showing that we could change an eye’s color. These rabbits don’t’ have blue eyes, but what we showed is we could (safely) remove the pigment.”

In 2009, Dr. Homer and his colleagues raised $2 million in a Series A round to form the company, build a prototype laser device, and open a clinical trial. They achieved their goals, successfully treating 17 patients in Mexico with solid efficacy and no adverse events.

The Procedure

The Strōma Medical  procedure is non-invasive. It involves no incisions or injections of any kind. In fact, other than the use of a small device to help keep the patient's eyelid open during the procedure and the application of a mild topical medication, there is little or no contact with the patient's eye.

The patient sits in front of the Strōma  laser, and his or her head is stabilized. The patient is instructed to direct the untreated eye toward a tiny animation, located about one foot from the patient's eye, while the procedure is completed. The procedure is then repeated to treat the other eye.

The Strōma Medical Laser work station.

The treating physician will inform the patient when he or she may drive and return to work. In most cases, the patient should be able to do so shortly after the procedure. For the first week or so following the procedure, the irises will get darker. Thereafter, they will grow progressively lighter, revealing the underlying natural blue color. The full color change process should take two to four weeks following the procedure.

Where Does the Process Stand?

According to Dr. Homer, the Strōma Medical laser process, which takes about 30 seconds per eye,  is still being clinically tested before being released commercially, first outside of the U.S.

To date, the company has completed preclinical studies on 50 Dutch-belted rabbits, and clinical studies on 17 human subjects treated in Mexico. The company is preparing its’ first large-scale pilot clinical study in Costa Rica, involving about 20 patients. Following the successful completion of that pilot study, the company plans to treat about 100 additional patients in multiple countries and follow them for a predetermined length of time. 

The company plans to release the product when it and the governing regulatory bodies are satisfied with the safety and efficacy of the procedure. Due to the relative cost and complexity of releasing a cosmetic medical device in the United States, they expect to release the procedure outside the United States first. The order of release in the non-U.S. territories will depend upon the market demand and regulatory environment in each territory.

Remaining Questions

The technique appears to be non-invasive, safe, and  painless. The laser treats only the front of the iris and does not enter the pupil or treat any portion of the inside of the eye where the nerves affecting vision are located.

But several questions do remain:

1.What happens to the pigment debris that leaves the iris? Will that debris clog up the normal drainage channels in the front of the eye, which can in turn cause glaucoma?

Strōma Medical claims that the digested particles released by the process are too fine to cause glaucoma and can easily pass through the trabecular meshwork and out into the anterior chamber -- and that even if there were any complications, they would be short-term and easily remedied, including the use of a standard laser procedure - selective laser trabeculoplasty (SLT), commonly used to eliminate pigment from the trabecular meshwork that might contribute to a rise in intraocular pressure. However, a small risk still remains, and the remaining studies are intended to address that risk prior to commercial release.

2. Don’t the pigmentary layers of the iris provide ultra-violet and infrared light protection to the lens and the retina in the back of the eye? Won’t removal of one of the layers increase the likelihood of cataracts and increased retinal problems due to increased ultra-violet and infrared light exposure?

Dr. Homer acknowledges that naturally light eyes tend to be more sensitive to bright light. He explains, however, that light eyes are not only less pigmented on the front surface of the iris, but throughout the eye, including the retinal nerves in the back of the eye that respond to light.  Light sensitivity, he maintains, is the result of less retinal pigment, not less pigment on the front surface of the iris.  Because the procedure is limited to the removal of pigment from the front surface of the iris, its removal would not increase light sensitivity. Instead, the procedure is able to achieve something that nature does not – a light eye without light sensitivity.  

3. How much will the procedure cost?

According to Dr. Homer, the procedure would likely cost about $5,000 for both eyes in the U.S., but the physicians doing the procedure would set the price, not the company itself, and it would likely vary depending upon territorial demand curves and currency fluctuations.

4. What will be the costs to the ophthalmologists?

The financial model for the procedure will follow LASIK – the laser device (which will be sold or leased), a maintenance contract for the device, and a per-procedure fee. The pricing has not yet been determined, but the company expects the device and service contract to cost less than those for LASIK, and the per-procedure fee to cost more.

5. Have you estimated the size of the market? Perhaps using the tinted contact lens market as an example?

According to market research done by the company, the relevant potential worldwide market for manufacturers of eye color changing products will be those people who have dark eyes (brown or hazel), are affluent enough to afford the procedure cost, and are 20-60 years of age. When the market is mature, 10.2 million people worldwide could have their eye color changed each year.  The largest patient population for the Strōma Medical’s system may be in India and China, followed by Central and South America, Southern Europe, Japan, Korea, the Middle East, and the United States.

Further, the company believes that the market for permanent eye color change will be the fastest growing segment of the aesthetics market over the next ten years. The market will be made up of individuals who have the money and the desire to change their eye color. The annual sustainable, and achievable market opportunity for companies in this space is estimated to approach $2.9 billion in five years. For physicians and their clinics, the market opportunity could be $9.3 billion. Early adapters of the technology will come from the 25 million patients who currently wear colored contact lenses, and the estimated 70 million patients who have stopped wearing them for aesthetic, comfort or an adverse response reason. But, the market could be much larger as the consistency of the results and a positive safety profile is confirmed through solid clinical studies.

6. Finally, do you have any IP protection? What’s to prevent a laser manufacturer to build both a laser and a diagnostic and aiming system to compete directly with you - in fact, isn’t there an entity in Barcelona that is now providing the service?

The company has an extensive international patent portfolio, which includes international patents covering several critical elements of the laser device and patents in the U.S., Singapore, and Australia covering any method or system using any form of electromagnetic radiation to alter iris color. The company also has additional protection covering various ancillary features of the procedure, such as its proprietary iris mapping and tracking technology, scan pattern, and beam profile.

The company claims that the physician in Barcelona was using an off-the-shelf laser designed for laser iridotomy and posterior capsulotomy, which is ill-suited for iris color change. As a result, many patients were injured – the local medical societies opened an investigation, and the physician appears to have discontinued the procedure.

To obtain more information about the process and the Strōma Medical laser, please visit the company’s website at this link.


1. Story Behind the Song: ‘Don’t It Make My Brown Eyes Blue’
2. Brown to blue: Procedure changes eye color, Erin Boyle, Ophthalmology Business, July 2013

3. The theory of selective photothermolysis predicts that the selective thermal damage of a pigmented target structure will result when a sufficient fluence at a wavelength preferentially absorbed by the target is delivered during a time equal to or less than the thermal relaxation time of the target. ("Selective photothermolysis: Precise microsurgery by selective absorption of pulsed radiation", RR Anderson and JA Parish, Science, 220:524-527, 1983.)

4. Iris pigmentation and pigmented lesions: an ultrastructual study, Eagle RC Jr., Tran Am Ophthalmol. Soc., 1988;86:581-687.

5. Strōma Medical Website.

Friday, March 27, 2015

Avalanche Update 2: Avalanche and Univ. Of Washington Collaborate to Defeat Color Blindness

Avalanche Biotechnologies and the University of Washington Enter Into Exclusive License Agreement to Develop Gene Therapy Approach to Treat Color Blindness

As reported by NPR’s health blog, Shots, on March 25th, Avalanche Biotechnologies in Menlo Park and the University of Washington in Seattle announced a licensing agreement to develop the first treatment for colorblindness. The deal brings together a gene therapy technique developed by Avalanche with the expertise of vision researchers at the University of Washington.

"Our goal is to be treating colorblindness in clinical trials in patients in the next one to two years," said Dr. Thomas Chalberg, the founder and CEO of Avalanche. The company will be entering IND-enabling studies this year.

The agreement has its roots in a scientific breakthrough that occurred six years ago. That's when two vision researchers at the University of Washington used gene therapy to cure a common form of colorblindness in squirrel monkeys.

"This opened the possibility of ultimately getting this to cure colorblindness in humans," says Jay Neitz, who runs the Color Vision Lab at UW along with his wife, Maureen Neitz.

The company also announced, that outside of the scope of the license agreement, Drs. Jay and Maureen Neitz, faculty in the UW's Department of Ophthalmology and color vision deficiency (CVD) experts, have joined its Scientific Advisory Board. They will be technical advisors to the company on the science of vision.

"This agreement with the University of Washington and world-renowned vision scientists Drs. Jay and Maureen Neitz will help us further advance our goal of developing therapeutic products for the millions of people who suffer from CVD," said Dr. Chalberg. "Our proprietary technology enables us to target the retina through intravitreal adeno-associated virus delivery, presenting, for the first time, the opportunity to pursue previously untreatable ophthalmic conditions such as CVD."

Avalanche will build on gene therapy research conducted by the Neitz research team, who used gene therapy to confer color vision in two adult male squirrel monkeys that had been color blind since birth. This groundbreaking work demonstrating proof-of-concept for treating CVD was published in the journal Nature (1).

Curing color blindness involves delivering new genes to cells in the retina that respond to color. That's how Jay and Maureen Neitz cured the squirrel monkeys six years ago. But the technique they used involved a surgical procedure on the retina.

For people, they desired a nonsurgical approach, something that had eluded researchers for years. Then a team at the University of California, Berkeley found a way to deliver genes using a simple injection into the vitreous, the clear gel that fills most of the eyeball.

Avalanche Biotechnologies has been working to improve and commercialize the Berkeley technique, said Chalberg.

So, Avalanche will combine the CVD gene therapy approach discovered by Drs. Jay and Maureen Neitz, with the licensed technology from the University of California at Berkeley and improved by Avalanche which will allow treatment via an intravitreal injection, similar to how wet AMD treatments are currently delivered in ophthalmologist’s offices, in a simple in-office procedure.

(I described this latter new virus vector delivery system in an article written in June 2013 entitled: Gene Therapy in Ophthalmology Update 19: A New Virus Vector for Safer Delivery of Gene Therapies)

According to Dr. Samuel Barone, Avalanche’s Chief Medical Officer, in response to my query if they were going to use the specific Berkeley vector research that I wrote about in Update 19, Dr. Barone said, “We licensed that intellectual property from Berkeley, and it serves as the basis for the delivery.  However, we have improved and optimized the technology, in better cone-specific transduction and protein expression.”

About CVD/Color Blindness and Avalanche's Targeted Development Program

Color vision deficiency (CVD), also known as red-green color blindness, is among the most common genetic diseases. CVD affects approximately 8 percent of males and 0.5 percent of females, or more than 10 million people in the U.S alone. CVD is a visual impairment that impacts many aspects of everyday life, resulting in limitations in professional choices, compromised health and safety, and the inability to perform many activities of daily living.

A simulation from the Neitz lab of what color blindness looks like, with normal color vision on the left and red-green color blindness on the right.

Photopigments in the retina are crucial for perceiving color. People with normal color perception have three different types of photopigments. These photopigments are tuned to perceive either long wavelengths (red), middle wavelengths (green) or short wavelengths (blue), respectively.

The most common forms of CVD are due to genetic defects that lead to missing either the L-opsin (Type 1, or protan defects) or the M-opsin (Type 2, or deutan defects). Affected individuals have trouble distinguishing between red and green and between colors that contain red or green hues.

Ishihara plate, a typical test for red-green colorblindness.

Avalanche has two drug candidates targeting these areas. AVA-322 carries the gene for L-opsin and is being developed for the treatment of Type 1 color vision deficiency. AVA-323 carries the gene for M-opsin and is being developed for the treatment of Type 2 color deficiency.

Avalanche expects to file an IND in the second half of 2016 to support advancement of these drug candidates into clinical trials, using Avalanche’s breakthrough non-surgical intravitreal injection method to deliver genes directly to cone cells at the back of the eye. The company recently launched for patients with color blindness to receive information about the condition and potential research study opportunities.

To read more about Avalanche Biotechnologies and its research programs, please see:


1. Gene therapy for red-green colour blindness in adult primates, Mancuso, K. et al, Nature, 2009; 461:784-787.

Thursday, January 15, 2015

Oraya IRay Update 3: Oraya Now Operating at Nine European Centers and Partnership with Carl Zeiss Meditec

The last time I checked in on Oraya, in March 2013 (Oraya IRay Update 2: INTREPID Two-year Results Meet Primary Clinical Endpoint - Results in At Least 35% Fewer anti-VEGF Injections), the company had just announced the two-year results of the INTREPID clinical study, showing favorable results in requiring fewer anti-VEGF treatments to treat wet AMD.

With the recent announcement (January 7, 2015) of a collaboration agreement between Oraya and Carl Zeiss Meditec, to provide funding to Oraya over a period of up to two years for the implementation of Oraya's growth strategy, and a report of the three-year INTREPID safety results last September, I decided to publish this update.

First, the three-year INTREPID trial safety results.

The three-year safety results were presented on September 13, 2014, at a EURETINA seminar where physicians also discussed their clinical experiences treating patients with Oraya Therapy.

The three year safety evaluation consisted of detailed image analysis looking for the presence of microvascular changes related to radiotherapy. Although small localized changes were identified by the reading center in a quarter of the patients, they did not significantly affect vision.

Commenting on the INTREPID study, Professor Ian Rennie, Consultant Ophthalmologist and Professor of Ophthalmology and Orthoptics and International Expert in Treatments of Ocular Cancers at Sheffield Teaching Hospitals NHS Foundation Trust said, "Of the cases I reviewed that were identified by the study expert panel as having microvascular changes attributable to radiation, most cases were so subtle that I would consider them clinically insignificant."

The INTREPID study was the first to evaluate the safety and efficacy of Oraya Therapy in conjunction with as-needed anti-VEGF injections for patients with wet AMD, and is the only sham-controlled double-masked trial to assess stereotactic radiotherapy for wet AMD. The study met primary and secondary endpoints and showed that Oraya Therapy significantly reduces the need for anti-VEGF injections while maintaining vision in the presence of a favorable safety profile. A total of 21 sites in five European countries participated in the trial. Two-year results showed that a broadly inclusive cohort of previously treated Wet AMD patients continued to receive the benefits of a 25 % mean reduction in anti-VEGF injections over two years. Additionally, the targeted patient population maintained an impressive 45 % mean reduction in injections through the two-year visit, with stable vision.

In simpler terms, as explained by Oraya President and CEO Jim Taylor, “The INTREPID trial enrolled a broad spectrum of patients, with some diagnosed out to 3 years prior (average ~15-18 months), and including many who's disease process had progressed to central scarring and other related conditions. In this broad cohort, we saw the 25% reduction of injections with equivalent vision outcomes to the controls.”

Further, “In a subset of patients who had active leakage and lesions that had not grown so large as to extend outside the Oraya treatment zone, we saw the far more significant 45% reduction; and some suggestion of potential for positive vision benefit as well. This becomes our "target patient population" for commercial/clinical use, and it is important to note that our research suggests these patients make up 60%-70% of the patient population under wet AMD management in a typical clinic.”

These impressive results coupled with increasing interest from physicians and patients, have led the Heart of England NHS Foundation Trust to become the second NHS center to install the technology. Patient treatment at the Trust was due to commence in October 2014. The Heart of England closely follows the Royal Hallamshire Trust in Sheffield, which began offering this innovative therapy in July 2014. The commercial use of Oraya Therapy has been rapidly expanding in Europe, with the treatment available in a total of eight centers (see note below) across the United Kingdom, Germany and Switzerland. It is covered by insurance in all three countries.

“As we conclude this ground-breaking three-year study of Oraya Therapy, results are showing that treatment can, and is, maintaining patients’ vision while significantly enhancing their quality of life,” said JimTaylor. “This result, coupled with the rapid expansion of the availability of the Oraya Therapy in the UK, and indeed across Europe, makes this a very exciting time for the company.”

(Editor’s Note: As of January 2015, there are now nine centers treating patients; four in the UK, one in Switzerland, and four in Germany. See the company website for additional information.)

On January 7, 2015, Carl Zeiss Meditec AG and Oraya Therapeutics, Inc. (Oraya) jointly announced that the companies had entered into a collaboration agreement under which Carl Zeiss Meditec will provide funding to Oraya over a period of up to two years for the implementation of  Oraya's growth strategy, and in turn receive rights in the company reaching up to a majority stake after two years.

The Oraya Therapy is available commercially in Germany, the UK and Switzerland, and the collaboration is intended to accelerate and expand these initial European market developments. While specific terms of the agreement were not disclosed, the companies noted that Carl Zeiss Meditec will be making a meaningful strategic investment in Oraya, and that further opportunities to leverage the companies' respective technical and market expertise and resources will be reviewed.

In discussing the transaction, Dr. Ludwin Monz, President and CEO of Carl Zeiss Meditec AG, stated, "The current pharmaceutical treatment regimens for wet AMD are exceptionally costly and burdensome, and Oraya's unique therapy offers a significant potential to positively impact the management of this debilitating disease." He went on to add that, "ZEISS has a long tradition of bringing new and innovative technologies to the ophthalmic market, from the earliest slit lamps, to category leading products such as glaucoma field analyzers, Optical Coherence Tomography (OCT) and innovative femtosecond laser platforms. These types of technology innovations, all offering significant provider and patient benefits, are part of the core strategy of Carl Zeiss Meditec AG."

Commenting on the agreement, Jim Taylor, CEO of Oraya, stated, "It is exceptionally rewarding to have the support and validation that are inherent in this commitment by Zeiss, a company universally recognized for its commitment to excellence in science as well as in patient-focused and physician-focused products and innovations. As a result of this collaboration, we have effectively enhanced our potential to positively impact patient outcomes, while significantly reducing the therapy burden for clinicians and providers as well."

In the USA the Oraya IRay is still an investigational device and is not yet available for sale.

Wednesday, January 07, 2015

Iluvien Update 9: Additional Marketing Approvals; A New Ophthalmic Application; and An Interesting Human Interest Story

Since I last wrote about Iluvien back in September (Iluvien Update 8: Alimera Sciences Receives FDA Approval of Iluvien for Treatment of DME), when Alimera Sciences and pSivida announced the FDA approval of Iluvien for treating chronic DME, adding the U.S. to the approvals or pending approvals obtained in seventeen European countries – approved in thirteen and pending approval in an additional four others, the product has become commercially available in the UK and Germany and is scheduled to become available in Portugal shortly.

With the FDA approval, Iluvien should also become commercially available in the U.S. in early 2015.

In a recent news release, Dr. Paul Ashton, President and CEO of pSivida, said, "We continue to be pleased as Iluvien gains additional marketing approvals in Europe. We believe Iluvien’s efficacy and three-year duration make it an attractive treatment option for many DME patients, particularly in the U.S. where the drug has broader labeling."

In addition to the application of Iluvien for the treatment of DME licensed to Alimera, pSivida is independently developing the product for the treatment of posterior uveitis. The FDA recently cleared the company's Investigational New Drug (IND) application to treat posterior uveitis with its injectable, sustained-release micro-insert, permitting pSivida to move directly to two Phase III trials under which it would enroll a total of 300 patients. However, the FDA approval of Iluvien for DME opens up the potential for pSivida to seek FDA approval on Medidur for uveitis with only one Phase III clinical trial, similar to what occurred with Allergan’s Ozurdex and its FDA approvals. The FDA is allowing pSivida to reference much of the data, including the clinical safety data, from the clinical trials of Iluvien for DME previously conducted by Alimera. Under the terms of its collaboration agreement with Alimera, pSivida has joint ownership of, and reference rights to, all clinical data and regulatory filings generated by Alimera, including its New Drug Application (NDA) for DME.

pSivida’s injectable micro-insert (Medidur) to treat posterior uveitis is a tiny tube about the size of an eyelash. It releases the off-patent steroid fluocinolone acetonide at a consistent rate over a period of approximately 36 months. The micro-insert is injected into the back of the eye during an office visit through the use of a fine gauge needle.

And, An Interesting Human Interest Story

What caught my attention, and brought me back to Iluvien (and the company, pSivida, that produces it and licenses it to Alimera Sciences for marketing) was a story that recently appeared in the Kansas City Star:

This is a story about a software engineer from Olathe, Kansas.

David Jiang was in danger of losing vision in his left eye when his eye specialist tracked down the inventor of a tiny eye implant that releases an anti-viral drug.

Jiang was examined recently by Siddhartha Ganguly (left) at the University of Kansas Cancer Center. 

David Jiang (left) says his vision remains slightly blurry but his retina is recovering after receiving the implant.

A year ago, after a routine physical, Jiang got the disturbing news that he had leukemia.

"I was shocked," he said, when his doctor called him with the diagnosis. His life was in danger, the doctor warned him. Jiang had been heading out the door to lunch. He changed his destination to the University of Kansas Cancer Center. The next morning, he started chemotherapy.

But the chemo wasn't doing the job of ridding Jiang's body of his cancerous bone marrow and the abnormal white blood cells they were producing. Doctors decided he needed a bone marrow transplant, a tough and sometimes risky course of treatment. A bone marrow donor was found, and Jiang received the transplant in April.

So, what does this have to do with Jiang's eyesight?

Before cancer patients undergo a bone marrow transplant, they must go through a rigorous course of chemotherapy or radiation to eliminate their own diseased marrow from their bones. The donated marrow is infused into their bloodstream and migrates to their bones, where it grows and begins producing healthy blood cells.

But bone marrow cells are also the source of the body's immune system. Until new marrow can renew patients' immune systems, they're exceedingly vulnerable to all kinds of infections. And as with other kinds of transplants, there's the potential for rejection, which can slow recovery.

When kidneys, livers and other organs are transplanted, the immune system of their new owner may sense them as foreign objects and launch a search and destroy mission. But with bone marrow transplants, rejection comes with a twist. It's the bone marrow itself, the person's new immune system, that sees its new home as the alien and attacks the patient. It's called graft versus host disease.

That's what happened to Jiang. "After the transplant, I was exhausted," he said. "I had one complication after another." There were headaches and stomach pain. To keep his graft versus host reaction in check, Jiang had to take drugs to suppress his immune system.

And that is how his eyesight was put in jeopardy.

Like most adults, Jiang is a carrier of cytomegalovirus, also called CMV. It's scary-sounding, and the virus can be life-threatening. But people with healthy immune systems generally keep it in check and never know they carry it. But in people with compromised immune systems, such as those with AIDS or bone marrow transplants, cytomegalovirus can cause big trouble.

Depending on which organs CMV attacks, it can cause inflammation of the brain, seizures, coma, ulcers in the digestive tract, pneumonia or inflammation of the liver. The virus also can attack the eyes.

For Jiang, it began a painful attack on the retina of his left eye, blurring his vision.

"We needed to stop this virus where it was or it was going to eat away the center of his vision," said Ajay Singh, Jiang's eye specialist at the University of Kansas Hospital. Singh started twice weekly injections of an anti-viral drug (ganciclovir) directly into Jiang's eyeball. The injections were painful and risked causing an infection. Singh couldn't give Jiang an oral version of the drug because it could damage his new bone marrow.

But Singh knew that during the AIDS epidemic, CMV eye infections were so common that a tiny device was created that could be loaded with medication and implanted directly into a patient's eye where it would slowly release the drug. Singh wanted one of these implants for Jiang - his patient was an ideal candidate - but they were nowhere to be found. It turned out that AIDS treatment had advanced so far that people with AIDS no longer were developing CMV eye infections. The implant manufacturer had pulled it off the market about a year or two ago, he found.

Singh was worried: The infection was a millimeter from the center of vision of Jiang's retina. If he didn't get an implant within a month, his vision could be lost. "The odds were stacked against him."

Early in October, Singh started making calls to Singapore, India and Mexico City, searching for an implant. He emailed the CEO of the company that discontinued the device but never received an answer. Eventually, the people Singh was contacting told him of an eye doctor in Kentucky who knew the original inventor of the implant. The Kentucky doctor put the two in touch. And it is here that the inventor-entrepreneur enters the picture.

"Dr. Singh somehow rooted me out," said Paul Ashton, CEO of Massachusetts-based pSivida. While pSivida had licensed its CMV implants to another company, it was still making other drug-dispensing eye implants.

Its newest is the size of an eyelash and can hold enough medication to treat diabetic eye disease for three years. Ashton offered Singh a slightly larger implant, about the size of a grain of rice, that would hold enough of the ganciclovir anti-viral drug.

"It was simply a matter of putting in a different drug," Ashton said. "We were changing the ammunition but keeping the same gun."

Singh recalled Ashton saying: "If you can send me the drug and get approval from the Food and Drug Administration, I will make you the implant." So Ashton went to his laboratory, testing the permeable ends of the tiny tube to be sure they would allow the drug to ooze out at the right speed. "It was a month of many sleepless nights. It was a race against time," Ashton said. "You can't keep injecting someone in the eye. Something bad is going to happen." Singh marveled at the speed with which Ashton's laboratory worked. "It's not like a car engine part" off the shelf, Singh said. "They have to test it. To do it in four weeks is a big deal."

In early November, the implant was ready. Singh called the FDA for emergency approval for the implant. "The FDA responded at lightning speed," he said. "I got an answer in four hours."

On Nov. 5, Singh implanted the device in Jiang's eye at KU Hospital.

"Now his cancer doctors can keep working on getting his bone marrow up and running," Singh said. The implant will continue delivering the drug to Jiang's eye for nine months to a year. "By that time, his immune system can recover and get the virus under control again."

Jiang said his vision is still a bit blurry, but his retina is recovering. Singh has assured him that in a few months, with new prescription glasses, he will be seeing well again. So far, his cancer hasn't returned and his graft versus host disease is well-controlled.

Jiang is grateful to the far-flung team that saved the vision in his left eye. "They all worked together. They worked so well together. I'm so fortunate."

To read more about how the pSivida drug delivery system works, please take a look at my initial writeup of Iluvien: Iluvien and the Future of Ophthalmic Drug Delivery Systems.


Tiny device and lots of teamwork save Olathe leukemia patient's sight, Alan Bailey, The Kansas City Star, January 2, 2015.