Evaluation of Performance and Safety of Carbopol 980 NF 0.2%- Based Medical Device in the Management of Patients With Glaucomar or Ocular Hypertension and Concomitant Dry Eye Syndrome on Multiple Long-term Topical Hypotensive Therapy

Evaluation of Performance and Safety of IRIDIUM® A Gel Preservative-free Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension and Concomitant Dry Eye Syndrome on Multiple Long-term Topical Hypotensive Therapy: a Prospective, Multicentric, Open-label Clinical Investigation.

The main aim of this investigation is to evaluate the effect of the preservative-free ophthalmic solution IRIDIUM® A gel on the ocular surface of patients with glaucoma or OHT and concomitant DES under multiple long-term topical hypotensive therapy for at least 6 months. The underlying assumption is that ophthalmic solutions as adjuvants for the management of IOP- or glaucoma-associated dry eye may induce a protection of the eye surface with consequent improvement of the symptoms and of the overall quality of life.

IRIDIUM® A gel is a sterile, preservative free ophthalmic gel, containing Carbopol, amino acids, Echinacea and Aloe extract. IRIDIUM® A gel is indicated for the protection of the eye surface particularly at night, even in the presence of changes in histological continuity and blepharitic conditions, including those of an iatrogenic nature, following the use of hypotonic eye drops and of the preservatives contained therein.

The main component of IRIDIUM® A gel is the Carbomer Carbopol 980 NF, a water-soluble polyacrylic acid with good mucoadhesion. It gives the gel the chemical-physical properties of viscosity and elasticity necessary for proper lubrication of the eyelids, forming a stable fluid film on the outer eye it provides protection to the eye surface, particularly at night.

The first approach to treat patients with ocular surface diseases relies on the use of artificial tears. Tear substitutes increase the volume of fluid on the ocular surface, thus reducing cell damage. Indeed, they induce a decrease in the osmotic pressure of the tear film and of the friction caused by eyelid movements.

For this, aqueous gels formulated using hydrophilic polymers along with those based on stimuli responsive polymers (in situ gelling or gel forming systems) continue to attract increasing interest for various eye health-related applications. Among these, eye drops containing carbomers or sodium hyaluronate are increasingly being used because of their non-Newtonian time-dependent response to shear strain, resulting in a longer ocular residence time.

Dry eye can also occur following specific treatments. In this regard, has been reported that dry eye symptoms are more prevalent in patients with IOP and/or glaucoma using topical IOP-lowering medications compared to the general population.

The evidence from literature suggests that different topical anti-IOP/glaucoma medications have different levels of impact on the health of the ocular surface. The main driver for this observation is the presence of preservatives in topical IOP-lowering medications. Generally, preservative-free medications have fewer adverse effects compared with preserved medications. However, the presence of preservatives, such as benzalkonium chloride (BAK), in antihypertensive eye drops used for long term therapy can cause ocular discomfort symptoms in glaucoma patients. BAK reduces the stability of the tear film by acting as a detergent on the lipid layer, by reducing the number of mucin secreting goblet cells, thus altering mucin presence and distribution over the ocular surface epithelium.

Clinicians need to take proactive decisions to manage ocular surface diseases of glaucoma patients as they are serious, chronic conditions. Previous findings confirm that glaucoma patients have a higher need for the use of artificial tears than age-matched controls , emphasizing that patients with ocular surface disease secondary to the chronic use of antiglaucoma medications should be preferably treated with preservative-free artificial tears.

Inclusion Criteria:

1. Have an age ≥ 18 years,;

2. Have undergone the informed consent process and have signed an approved consent form;

3. Are able to comprehend the full nature and the purpose of the investigation, including possible risks and side effects, and subjects able to cooperate with the Investigator and to comply with the requirements of the entire investigation (including ability to attend all the planned investigation visits according to the time limits), based on Investigator's judgement;

4. Have a diagnosis of glaucoma or Ocular Hypertension (OHT). Diagnosis of glaucoma will be based on: optic disc assessment, measurement of the retinal nerve fiber layer and neuroretinal rim with optical coherence tomography (OCT); characteristic repeatable visual field defects defined as a pattern standard deviation (PSD) with P < 0.05, and/or glaucoma hemifield test (GHT) results outside normal limits. Diagnosis of OHT will be based on history of IOP (intraocular pressure) > 21 mmHg in at least two occasions and normal optic disc and Humphrey visual field test;

5. Are receiving an ongoing topical therapy with two or more preserved ocular hypotensive agents (e.g. beta-blockers, alpha-agonists, carbonic anydhrase inhibitors, prostaglandins) for at least 6 months and are willing to continue these treatments at unchanged dose for the entire investigation duration;

6. Have a diagnosis of moderate to severe DES performed through the following exams: slit lamp examination (SLE), tear (lacrimal) meniscus exam, Schirmer's test, Tear Film Break-Up Time (TFBUT), fluorescein staining of the cornea and conjunctiva (Oxford Staining Scheme). Please note that a diagnosis of DES may be performed at entry in the investigation;

7. Have a Tear Film Break-Up Time (TFBUT) value < 7 sec;

8. Have performed a Humphrey Visual Field Test in the last 4 months, if not available the test will be performed during the screening visit;

9. In case of females of child-bearing potential (i.e., not permanently sterilized - post hysterectomy or tubal ligation status - or not postmenopausal), they must have a negative urine pregnancy test at T0 and use a reliable form of contraception for a least 1 month prior to T0 and throughout the investigation, according to the definition of Note 3 ofICH M3 Guideline*.

   • Note: According to the definition of Note 3 of ICH M3 Guideline a highly effective method is defined as those which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Highly effective birth control methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence.

Exclusion Criteria:

1. Best corrected visual acuity score < 20/40;
2. Ischemic oculopathy;
3. Contraindications to use of topical solution components used in this investigation or known allergy/hypersensitivity to any of the IRIDIUM®A gel ingredients;
4. Current use/use in the past 15 days of any ocular medications other than hypotensive eye drops;
5. Systemic treatments known to affect tear secretion;
6. Treatment with any other therapy that, according to Investigator's judgment, could interfere with the assessment of the efficacy or incidence of adverse events;
7. Any history or slit lamp evidence of eye surface diseases different from DES;
8. History of ocular trauma or surgery in the past 12 months;
9. History of cataract in the past 6 months;
10. Any history of corneal refractive surgery;
11. Use of systemic steroids or immunosuppressants;
12. Participation in another clinical study/investigation at the same time as the present investigation or within 30 days;
13. History of drug, medication or alcohol abuse or addiction;
14. Pregnant (positive urine pregnancy test) or breastfeeding women, or women planning to become pregnant during the investigation