Effects of Topical Low Dose Preservative-free Hydrocortisone on Intraocular Pressure

Effects of Topical Low Dose Preservative-free Hydrocortisone on Intraocular Pressure in Patients With and Without Glaucoma

Evaluation of the safety and efficacy of hydrocortisone eye drops in the treatment of OSD (ocular surface disease) patients with and without glaucoma.

Study Overview

• Status: Completed
• Conditions: Glaucoma; Ocular Surface Disease
• Intervention / Treatment: Drug: Hydrocortisone (CORTIVIS ®)

Detailed Description

The ocular surface comprises the cornea, conjunctiva, eyelids and lacrimal glands and any disorder in these structures can be classified as an ocular surface disorder (OSD). OSD includes Dry Eye Disease (DED), blepharitis and meibomian gland dysfunction (MDG), allergic eye diseases (AED), chemical and thermal burns; all these conditions can severely affect eyesight and quality of life, and sometime even blindness. Patients with OSD can develop photophobia, corneal scarring, intermittent blurred vision, pain, limited ability to perform daily activities, reduced vitality, poor general health and, in many cases, depression.

Glaucoma, one of the leading causes of irreversible blindness, is an optic neuropathy characterized by thinning of retinal nerve fiber layer and increase of optic disc cupping , whose main risk factor is closely related to the intraocular pressure (IOP) levels. Thus, the management of the disease consists in the lowering IOP through medical, laser or surgical therapy . However, IOP reduction is most commonly achieved using topical ocular medications, which often contain preservatives employed to maintain stability and sterility of the product. Preservatives can be associated with undesirable adverse effects such as allergy, local irritation and inflammation . The long-term use of anti-glaucoma medications produces several alterations of ocular surface components, especially at the conjunctival level where epithelial modifications, dendritic cell activation, conjunctiva-associated lymphoid tissue activation, and goblet cell (GCs) loss easily occur GCs play crucial tasks in the homeostasis of the ocular surface being the main source of mucoproteins, essential to maintain tear film stability. Thus, the loss of GCs progressively leads to the happening of an iatrogenic OSD . Moreover, advancing age is a significant risk factor for both OSD and glaucoma, further complicated by treatments for each condition, which can interact among them and yield counterproductive effects . For these reason glaucoma is often associated with OSD .Ocular surface inflammation is crucial in the pathophysiology of OSD, therefore anti-inflammatory therapy, including corticosteroids, may be of benefit to OSD patients . However, in susceptible individuals steroid-induced glaucoma or ocular hypertension can occur after steroid use. Individuals who develop an increase in IOP following steroid use are referred to as "steroid responders" . In a recent study Kallab et al. have found that dry eye treatment with low hydrocortisone dose reduced ocular inflammation without inducing increases in IOP ; glaucomatous patients were excluded from this study. Herein we evaluate the safety and efficacy of hydrocortisone eye drops in the treatment of OSD patients with and without glaucoma.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Campobasso, Italy
    • University of Molise

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age of at least 18 years
• diagnosis of OSD (Ocular Surface Disease)
• normal ophthalmic findings except history of OSD for at least 3 months, and current therapy with topical lubricants for at least 3 months
• POAG (primary open-angle glaucoma ) patients on medical therapy

Exclusion Criteria:

• clinically significant slit lamp findings at screening visit except OSD
• participation in a clinical trial in the 4 weeks preceding the screening visit
• symptoms of a clinically relevant illness in the 3 weeks before the screening visit
• presence/ history of a severe medical or surgical condition
• intake of parasympathomimetic or antipsychotic drugs
• wearing of contact lenses
• previous refractive laser surgery (e.g photorefractive keratectomy-PRK, laser assisted in situ keratomileusis-LASIK, etc.)
• history of IOP increase caused by systemic or topical treatment with corticosteroids
• IOP greater than 22 mmHg
• treatment with corticosteroids in the 4 weeks preceding the study
• types of glaucoma other than POAG
• ocular infection or clinically significant inflammation
• ocular surgery in the 3 months preceding the study
• Sjögren's syndrome, Stevens-Johnson syndrome
• history of allergic conjunctivitis
• pregnancy, planned pregnancy or lactating
• known hypersensitivity to any component of study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: glaucoma; OSD patients with glaucoma	Drug: Hydrocortisone (CORTIVIS ®); Once enrolled all the patients had to instill topical low dose (1,005 mg) preservative-free hydrocortisone (CORTIVIS ®- Medivis, Catania, Italy) 2 times daily in each eye for two weeks.
Active Comparator: Group B: no glaucoma; OSD patients without glaucoma	Drug: Hydrocortisone (CORTIVIS ®); Once enrolled all the patients had to instill topical low dose (1,005 mg) preservative-free hydrocortisone (CORTIVIS ®- Medivis, Catania, Italy) 2 times daily in each eye for two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular pressure(IOP)	IOP evaluation at time zero (T0), after 1 (T1) and two weeks of therapy (T2).	2 weeks
OSDI (Ocular Surface Disease Index) questionnaire	OSDI record at time zero (T0), after 1 (T1) and two weeks of therapy (T2).	2 weeks

Collaborators and Investigators

• Sponsor: University of Molise
• Collaborators: Medivis

Publications and helpful links

General Publications

• Craig JP, Nelson JD, Azar DT, Belmonte C, Bron AJ, Chauhan SK, de Paiva CS, Gomes JAP, Hammitt KM, Jones L, Nichols JJ, Nichols KK, Novack GD, Stapleton FJ, Willcox MDP, Wolffsohn JS, Sullivan DA. TFOS DEWS II Report Executive Summary. Ocul Surf. 2017 Oct;15(4):802-812. doi: 10.1016/j.jtos.2017.08.003. Epub 2017 Aug 8.
• Khanna RC. Ocular surface disorders. Community Eye Health. 2017;30(99):S1-S2. No abstract available.
• Lanza M, Gironi Carnevale UA, Mele L, Bifani Sconocchia M, Bartollino S, Costagliola C. Morphological and Functional Evaluation of Oral Citicoline Therapy in Chronic Open-Angle Glaucoma Patients: A Pilot Study With a 2-Year Follow-Up. Front Pharmacol. 2019 Sep 26;10:1117. doi: 10.3389/fphar.2019.01117. eCollection 2019.
• Mohammed I, Kulkarni B, Faraj LA, Abbas A, Dua HS, King AJ. Profiling ocular surface responses to preserved and non-preserved topical glaucoma medications: A 2-year randomized evaluation study. Clin Exp Ophthalmol. 2020 Sep;48(7):973-982. doi: 10.1111/ceo.13814. Epub 2020 Jul 27.
• Rossi GC, Pasinetti GM, Scudeller L, Bianchi PE. Ocular surface disease and glaucoma: how to evaluate impact on quality of life. J Ocul Pharmacol Ther. 2013 May;29(4):390-4. doi: 10.1089/jop.2011.0159. Epub 2012 Dec 7.
• Rossi GC, Pasinetti GM, Scudeller L, Raimondi M, Lanteri S, Bianchi PE. Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients. Eur J Ophthalmol. 2013 May-Jun;23(3):296-302. doi: 10.5301/ejo.5000220. Epub 2012 Dec 17.
• Kallab M, Szegedi S, Hommer N, Stegmann H, Kaya S, Werkmeister RM, Schmidl D, Schmetterer L, Garhofer G. Correction to: Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial. Adv Ther. 2020 Jan;37(1):342-343. doi: 10.1007/s12325-019-01190-3.
• Filippelli M, dell'Omo R, Gelso A, Rinaldi M, Bartollino S, Napolitano P, Russo A, Campagna G, Costagliola C. Effects of topical low-dose preservative-free hydrocortisone on intraocular pressure in patients affected by ocular surface disease with and without glaucoma. Graefes Arch Clin Exp Ophthalmol. 2022 Jan;260(1):247-253. doi: 10.1007/s00417-021-05345-3. Epub 2021 Aug 18.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Actual): March 4, 2020
• Study Completion (Actual): March 4, 2020

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: CTS 11/2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No