Clinical Investigation on the Use of Ophthalmic Solution Based on Sodium Hyaluronate in Treatment of Eye Discomfort

The TFBUT will be performed after instillation of 5 microliters of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient will be instructed to blink several times to thoroughly mix the fluorescein with the tear film. To achieve maximum fluorescence, the examiner should wait approximately 30 seconds after instillation before evaluating TFBUT. The TFBUT was measured by determining the time in seconds to tear break-up within 10 seconds maximum, and it was measured three time during the first minute after the instillation of fluorescein solution. The TFBUT value will be the average of 3 measurements.

Time frame: Evaluated at Visit 1 (baseline) and Visit 3 (day 35 ± 4 - study termination)

Population: A total of 28 patients were screened and included in the FAS (ITT analysis) and in the Safety population. Three out of 28 patients had a major protocol deviation, one patient did not show up for the study termination visit, two patients did not meet the exclusion criteria Taking drugs that may interfere with tear gland secretion (beta -blockers). Thus, the PP population consisted of 25 patients.

The ETDRS chart uses a standardized, logarithmic letter chart (Sloan letters, 5 per line). Results can be reported as either logMAR values or letter scores, in our study we used the Line method (the smallest line where at least 3 of 5 letters are correctly read), while Visual Acuity was expressed as Snellen Distance Equivalent (meters); in the Italian decimal system, 10/10 corresponds to 6/6 or 0.0 logMAR. To maintain consistency across clinics and trials, the examination conditions were standardized as follow: Test distance 4 meters, Chart uniformly illuminated (\ 85 cd/m² luminance), with a white, high contrast (≥ 90%) background, the Best corrected visual acuity (BCVA) was measured with trial frame lenses. The BCVA was testing monocularly, while the patient was encouraged to read as many letters as possible, even if guessing. When the patient misses a prespecified number (3 or more errors in a row), testing stops.

Time frame: Evaluated at day 14± 2 and 35 ± 4 of treatment versus baseline

Quality of life was assessed using the Dry Eye-Related Quality of Life Score (DEQS) questionnaire, which includes 15 items grouped into two subscales: Symptom Burden (6 items) and Impact on Daily Life (9 items). Each item is scored on a 0 to 4 scale, with higher scores indicating worse symptoms. Subscale scores range from 0 to 24 and 0 to 36, respectively. A total DEQS score was calculated by summing all item scores and converting the raw total to a 0-100 scale, where lower scores indicate better quality of life.

Time frame: Baseline (Visit 1) and Study Termination Visit (Day 35 ± 4)

To evaluate the degree of satisfaction of patients to the treatment we used the visual analogue scale (VAS) ranging from 0 to 100 mm in a horizontal line. Patients will be asked to place a vertical mark (on the horizontal line, from 0 to100 mm) to indicate the degree of satisfaction to the treatment, where: 0-10 mm=no: 1-30 mm=very mild; 31-50 mm=mild; 51-70 mm=moderate; 71-90 mm=strong; 91-100 mm=very strong. Patients were asked to rate their level of satisfaction answering each of these questions: 1) I feel satisfied using this treatment? ''; 2) With this treatment, I have a feeling of freshness?; 3) With this treatment, I have a feeling of relief?; 4) This treatment contributed to reduce my pain due to eye dryness?''; 5) This treatment is comfortable? '' The response results are expressed in frequency and percentage of the total for each of the questions in the categories very mild, mild, moderate, strong and very strong.

Time frame: Evaluated at day 35 ± 4 of treatment

Population: Frequency missing = 1

The NEI/Industry Workshop scale (1995) is an ophthalmological rating scale developed by the National Eye Institute (NEI, USA) to measure the degree of corneal and conjunctival staining after instillation of fluorescein or rose bengal/lissamine green. * The cornea is divided into 5 zones: Central, Superior, Inferior, Nasal, Temporal. Each zone is assigned a score from 0 to 3: 0 = no staining; 1 = mild; 2 = moderate; 3 = severe (Lower values=better outcomes - Total maximum cornea staining = 15). * The bulbar conjunctiva is divided into 6 areas: Superior nasal, Inferior nasal, Superior temporal, Inferior temporal, Superior (under the upper eyelid, less frequently assessed), Inferior (above the inferior fornix). The total maximum conjunctiva staing is 18. The total staining score is given by the sum of the corneal and conjunctival staining (Lower values=better outcomes - Min=0, Max=33).

Time frame: Evaluated at Visit 1 (baseline), Visit 2 (day 14± 2) and Visit3 (day 35 ± 4 - study termination visit)

The SANDE questionnaire (Symptom Assessment in Dry Eye) is a very simple, validated tool to assess dry eye symptoms. It's based on two visual analog scale (VAS) questions that measure: 1) Frequency of symptoms (dry and irritated); 2) Severity of symptoms (dryness and irritation). Each question is scored by the patients on a 0-100 mm VAS line (0 = no symptoms, 100 = maximum symptoms), marking the point that they feel represents their perception of their current state. Data collected from the SANDE questionnaire were calculated by multiplying the frequency score by the severity score and obtaining the square root.

Time frame: Evaluated at Visit 1 (baseline), Visit2 (day 14± 2) and Visit3 (35 ± 4 - study termination)

The TFBUT will be performed after instillation of 5 microliters of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient will be instructed to blink several times to thoroughly mix the fluorescein with the tear film. To achieve maximum fluorescence, the examiner should wait approximately 30 seconds after instillation before evaluating TFBUT. The TFBUT was measured by determining the time in seconds to tear break-up within 10 seconds maximum, and it was measured three time during the first minute after the instillation of fluorescein solution. The TFBUT value will be the average of 3 measurements.

Time frame: Evaluated at day 14 ± 2 of treatment (Visit 2) and day 35 ± 4 of treatment (Visit 3 - Study termination)

Population: A total of 28 patients were screened and included in the FAS (ITT analysis) and in the Safety population. Three out of 28 patients had a major protocol deviation, one patient did not show up for the study termination visit, two patients did not meet the exclusion criteria Taking drugs that may interfere with tear gland secretion (beta -blockers). Thus, the PP population consisted of 25 patients.

Intraocular pressure (IOP) was measured in mmHg using Goldmann applanation tonometry after topical anesthesia with unpreserved 0.4 percent oxybuprocaine hydrochloride. IOP was assessed at three pre-specified study visits: baseline (Visit 1), Visit 2 during treatment, and the Study Termination Visit. Results were summarized by visit for all participants included in the intention-to-treat population.

Time frame: Baseline (Visit 1), Visit 2 (Day 14 ± 2), and Study Termination Visit (Day 35 ± 4)

Safety was assessed using the Investigator Global Assessment of Safety (IGAS), a 4-point categorical scale where 1 = very good safety, 2 = good safety, 3 = moderate safety, and 4 = poor safety. IGAS was evaluated at the Study Termination Visit and summarized by reporting the number and percentage of participants in each category.

Time frame: Study Termination Visit (Day 35 ± 4)

Population: One patient did not show up to study termination visit

Treatment compliance was assessed during the treatment period by counting returned single-dose containers and boxes at the Study Termination Visit. Compliance was calculated as the percentage of prescribed doses administered relative to planned doses for each participant. Participants were categorized into predefined compliance categories (\<50%, 50-80%, \>80%) for reporting purposes.

Time frame: During the treatment period, assessed at Study Termination Visit (Day 35 ± 4)