Clinical Trials

Every year brings promising advances for people living with sight loss. At present, there are many clinical trials underway for inherited retinal degenerations including retinitis pigmentosa (RP), Stargardt disease, Usher syndrome, Leber congenital amaurosis (LCA), Leber hereditary optic neuropathy (LHON), X-linked retinoschisis, choroideremia and achromatopsia. Additional trials are also taking place for dry and wet forms of age-related macular degeneration (AMD) and diabetic retinopathy. Some of the approaches being studied in these trials include gene therapies, cell-based therapies, neuroprotective molecules, anti-VEGF drugs, RNA therapies and implant devices. To learn more about what is involved in a clinical trial, please read on.

In this Section:

What is a clinical trial?

Clinical trials are an extremely important stage of the research and development process. Continuing on from positive observations in the lab, they serve as an essential extension of this pre-clinical work and investigate the safety and efficacy of a potential intervention in humans. At this stage, we use the word “intervention” instead of the word “treatment”. This is because these approaches are still being studied for safety and efficacy and are not yet established or recognised therapies. Examples of  interventions include drug compounds, gene replacement, cell based approaches, devices, surgical techniques, delivery systems and diet, to name but a few.

Clinical Trial Phases:

We can think of a clinical trial as a racehorse on the day of a big race. Each racehorse will have to jump a number of fences successfully before reaching the finish line. Similarly, each clinical trial will have to pass a number of hurdles, or phases, before it can be used in clinical practice. The earlier phases of a clinical trial test how safe the intervention is, while latter stages test how effective it is. Each phase must be completed before moving on to the next.

Phase I

A Phase I study is focused on safety, ensuring that the potential intervention does no harm or results in any dangerous side effects. They are usually small trials, recruiting less than thirty patients. For rare diseases such as inherited retinal degenerations, the number of participants can be even smaller. Individuals recruited to Phase I trials often have an advanced form of the condition. This is to ensure that any potential adverse effects on sight will be limited as much as possible. Investigators may also test increasing doses of a treatment in different patient groups, often referred to as dose escalation, to identify the maximum tolerable level. Unfortunately, not all interventions will progress from Phase I to a Phase II.

Phase II

A Phase II study retains the major focus on safety but also begins to evaluate efficacy in a larger number of individuals. For rare diseases, this may still be a small group of participants. In some cases, the intervention may be compared against a treatment currently in use. In other cases, it may be tested against a non-functional intervention (known as a placebo or “sham” treatment). A phase II is likely to take two to four years.

Phase III

A Phase III study is the final, or “pivotal,” stage before seeking regulatory and marketing approval from the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). In this phase, investigators are looking for strong evidence of efficacy. The therapy may be studied at multiple clinical sites to determine if investigators can achieve the same results independently.

Combined Phases
For many emerging therapies targeting rare conditions, phases are combined. For example, Phase I and II can be combined as a Phase I/II, or Phase II and III as a Phase II/III. This is done to save time and money but also to accommodate the limited number of participants available for the clinical trial.

Phase Four

Phase Four studies are performed after an intervention has been clearly shown to be safe and effective and has been granted a license. They are performed to understand more about the intervention by evaluating its safety and effectiveness in larger numbers of patients, subgroups of patients, and to compare and/or combine it with other available treatments.

Things to Consider:

  1. We must remember that a clinical trial is still an experiment and as such comes with risks. There are no guarantees that a study participant will receive any direct benefit from being on a clinical trial. For example, in the early stages of testing, the dosage of the intervention may be much lower than what is expected to be effective in treating the condition. This is because the first goal is to establish that the intervention is safe for people to take.
  2. Also, it may be the case that in some trials, participants may not actually be treated. Instead, they will get a ‘placebo’ and won’t know whether they have received the placebo or intervention until the study concludes. Those who get the placebo are still helping to advance the trial. As such, motivation for participating in a study should be to help advance the research.
  3. Unfortunately, not every racehorse will make it to the finish line. The same can be said for clinical trials – not every clinical trial will be successful and make it to the final stages. Some are lost through the various phases. This may be due to an intervention not having the desired benefit or it causing undesired side effects. Participation in a clinical trial also requires a significant time and personal commitment on the part of the individual and family. As such, people may drop out during the study. Another challenge facing clinical trials is difficulty in enrolling participants. This is particularly the case for rare diseases where prevalence of a condition may be low.
  4. As more sight loss diseases are addressed, clinical trials are likely to require special consideration with respect to outcome measures. “Outcome measures” are the tests that investigators perform to decide whether an intervention being studied in a clinical trial is having any beneficial effect. An improvement in visual acuity has been the primary outcome measure for many trials for retinal disease. However, for someone affected by an inherited retinal degeneration this may not be the most accurate or appropriate method of quantifying benefit. As this area advances, there is a greater need for clinical trials to measure things that are important, relevant and appropriate to patients (functional vision) and for participants to be able to give feedback on what they experience (patient reported outcome measures). A wonderful example of a carefully designed outcome measure is the multi-luminance mobility test (MLMT), designed by Spark Therapeutics. This is a maze that assesses a person’s mobility at different light levels. The evidence collected from this played a key role during the approval of LUXTURNA™, the first gene therapy for a rare eye disease.


How can you get involved in a clinical trial?

It’s important to understand that clinical trials have several inclusion and exclusion criteria for participants. One’s age, genetic profile, level of vision and medical history are all factors in determining eligibility for a study. If you would like to participate in a clinical trial, we advise that you start by speaking with your ophthalmologist. They will be in the best position to advise you on what options are available and if you are a suitable candidate for a trial. You are free to leave a trial at any time without obligation, and you will not need to explain your reasons for leaving.

In the case of inherited retinal degenerations, many therapies will rely on correcting the exact gene that is causing the condition. Thus one of the criteria for enrolling in a trial will be knowing the gene causing your condition. This is why our Target 5000 is so important. Target 5000 aims to identify the exact genetic profile of people affected by a retinal degenerative condition in Ireland. You can get involved in Target 5000 by contacting the Fighting Blindness Research Department on 01 6789 004 or


How can you find out more about clinical trials?

For information about clinical trials specific to your condition, please contact the Research Department on 01 6789004 or, who can provide up-to-date, relevant information tailored to your query.

To find clinical trials for a particular condition, treatment or country, provide a useful source of information.

For clinical trials within the European Reference Network-Eye Centre (ERN-EYE) membership, please visit where clinical trials can be identified by condition.