Year XXIII, N. 7, May 2020

Innovation in Ophthalmology

Treatment with Waterfall artificial tears in patients

with alterations and dysfunction of the cornea and lacrimal

apparatusDavid Ciacci, Francesca Jonsson

O

Year XXIII, N. 7, May 2020

Treatment with Waterfall artificial tears in patients with alterations and dysfunction of the cornea and lacrimal apparatus David Ciacci, Francesca Jonsson

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Contents

Abstract 2

Introduction 2

Objective 4

Materials and methods 4

Results 5

Conclusions 7

References 7

Treatment with Waterfall artificial tears in patients with alterations and dysfunction of the cornea and lacrimal apparatusDavid Ciacci1, Francesca Jonsson2

1 Head of Ophthalmology, Chiros Srl, Turin, Italy; Director of Ophthalmology Service, Cidimu Group SpA, Turin, Italy; IRR Rehabilitations Institute, Turin, Italy2 Orthoptist and Ophthalmic Assistant, Chiros Srl, Turin, Italy; Ophthalmology Service, Cidimu Group SpA, Turin, Italy; IRR Rehabilitations Institute, Turin, Italy

2

Treatment with Waterfall artificial tears in patients with alterations and dysfunction of the cornea and lacrimal apparatus

Abstract

The objective of this 3-month study was to

evaluate the effects of artificial tears in im-

proving the subjective symptoms and ob-

jective parameters of patients suffering from

tear dysfunction or corneal disorders.

The study was conducted on 11 subjects se-

lected from among patients with subjective

qualitative lacrimal disorders and corneal

dysfunction or alterations, such as corneal

dystrophies or pre-existing keratopathies,

either concomitant with systemic diseases

or following ophthalmological interven-

tions. The subjects used Waterfall tear re-

placement drops for a period of 90 days and

both subjective and objective assessments

were carried out in three successive steps

by means of specific tests and question-

naires.

The response and tolerance of the patients

who used Waterfall eye drops and benefit-

ed from the instillation was good, in terms

of both subjectively reported symptoms and

objective improvement of the corneal and

tear film parameters.

Introduction

Keratopathies represent a heterogeneous

group of non-inflammatory conditions

affecting the cornea; these may remain

asymp tomatic for a long time and therefore

go undiagnosed, or they may cause serious

subjective disturbances in patients with sec-

ondary lacrimal dysfunction. Keratopathies

may be congenital and be caused by gene

mutations, as in cornea guttata, or acquired

and/or concomitant to systemic diseases.

The corneal endothelium, the stroma and

the corneal epithelium are generally affect-

ed. The main symptoms reported by the pa-

tients are nonspecific and consist of ocular

dryness, increased blinking, photophobia,

foreign body sensation and general eye dis-

comfort[1].

In addition, dry eye is a common though fre-

quently under-recognized disorder whose

etiology and management constitutes a

challenge for both clinicians and research-

ers. Advances in the understanding of the

Treatment with Waterfall artificial tears in patients with alterations and dysfunction of the corneaand lacrimal apparatus

3

disease have been made over the past 10

years in areas of epidemiology, pathogen-

esis, clinical manifestations, and possible

therapy.

The most recent classification of dry eye dis-

ease (DED) is the one provided by the report

of the Definition and Classification Subcom-

mittee of the International Dry Eye Work-

shop (DEWS, 2007): “Dry eye is a multifac-

torial disease of the tears and ocular surface

that results in symptoms of discomfort, with

potential damage to the ocular surface. It is

accompanied by increased osmolarity of the

tear film and inflammation of the ocular

surface”[2].

In the latest update published in 2017, the

DEWS II defines it as a “multifactorial dis-

ease of the ocular surface characterized by

a loss of homeostasis of the tear film, and

accompanied by ocular symptoms, in which

tear film instability and hyperosmolarity,

ocular surface inflammation and damage,

and neurosensory abnormalities play etio-

logical roles”[3].

A summary of the data indicates that the

prevalence of dry eye ranges between 5-30%

in the population aged 50 years and older.

There is international agreement that the

prevalence of severe disease is most prob-

ably at the low end of this range while that

of mild or episodic disease is closer to the

upper end of this range[4].

Changes in visual performance in con-

junction with discomfort can contribute

to decreased quality of life (QoL) among

patients with DED[5]. As DED common-

ly presents as a foreign-body sensation,

burning or stinging, and/or photophobia, it

can contribute to blurred vision and contact

lens intolerance. Visual acuity after sus-

tained eye opening, or ‘functional’ visual

acuity (believed to simulate an individual’s

vision while reading, driving, and working

at a computer screen), appears specifically

impaired by DED.

Figure 1 and Figure 2 show examples of

dry eye.

Figure 1. Dry eye with stromal invasion of the vessels.

Figure 2. Dry eye.

4

Objective

The objectives of this study were to evaluate

the effects of artificial tears in improving the

subjective symptoms of tear dysfunction or

corneal disorders and thus the patients’ vi-

sual wellbeing and to establish whether this

improvement corresponded to an objective

improvement of the ocular parameters mea-

surable with diagnostic tests.

Materials and methods

The study was conducted on a sample of

11 patients suffering from congenital or ac-

quired corneal disorders (cornea guttata,

keratopathies, corneal dystrophies) and tear

alterations with serious subjective disorders.

The study participants were selected from a

sample of 25 patients who were examined

and interviewed so as to exclude those af-

fected by pathological conditions likely to

reduce cohort homogeneity or that might

interfere with the results.

The ophthalmologist (D.C.) collected the pa-

tients’ ophthalmological history and state-

ments, after having carried out a complete

ophthalmological examination comprising

slit-lamp biomicroscopy. He also performed

a series of diagnostic tests, including tear

film break-up time (BUT), endothelial cell

count, Schirmer’s test, meibography, and

tear osmolarity analysis.

The parameters assessed were the BUT test,

the endothelial cell count and the Ocular

Surface Disease Index (OSDI) score – all

measured at baseline and at the end of the

study – as well as an individual question-

naire administered at the end of the study.

The study had a total duration of 90 days

and was divided into three main steps:

• 1st visit (time 0), in which the patients un-

derwent complete eye examination, BUT

test, endothelial cell count and OSDI as-

sessment;

• 2nd visit (time 0 + 30 days), in which adher-

ence to therapy was assessed through an

eye examination and tolerance to the arti-

ficial tears through an interview, and the

correct use of the eye drops was verified;

• 3rd visit (time 0 + 90 days), in which the

patients underwent complete eye exam-

ination, BUT test, endothelial cell count

and OSDI assessment, in addition to

completing a patient satisfaction ques-

tionnaire on the use of the eye drops.

The BUT tests were performed using a

SIRIUS corneal topographer without the

use of fluorescein; the patient was asked to

blink twice and then to keep the eye open

for as long as possible. The endothelial cell

count was carried out using a computerized

no-contact instrument that analyzed endo-

thelial cell density and structure (polymega-

thism and pleomorphisms). The OSDI ques-

tionnaire was used to investigate the impact

of symptoms on the patient’s daily life.

The new Waterfall product is a multidose,

preservative-free, ophthalmic hypotonic gel

containing hyaluronic acid 0.4% and Kol-

liphor P407. It is a medical device that helps

Treatment with Waterfall artificial tears in patients with alterations and dysfunction of the corneaand lacrimal apparatus

5

Results

A total of 11 patients were studied over a pe-

riod of 90 days. Nine patients completed the

study; two patients discontinued treatment

after 1 month because of intolerance to the

eye drops attributed to their excessive stick-

iness.

The patient satisfaction questionnaire re-

vealed an overall subjective improvement

in all patients who used Waterfall gel drops,

with good tolerance and good compliance

with the product. In detail, 67% of patients

reported a marked subjective improvement

in symptoms and QoL, whereas 33% re-

ported only a relative improvement with no

change in symptoms compared with the be-

ginning of the study (Figure 3).

The results of the BUT test and endothelial

cell count showed an overall objective im-

provement of the ophthalmological param-

eters, with an increase in the BUT values

(Figure 4) and a slight increase in corneal

cell density in many patients.

to keep the eye hydrated and to protect the

ocular surface by forming a protective film.

Thanks to an innovative formulation, Wa-

terfall gel drops have thermo-thickening

properties: from an easy-to-instil, aqueous

solution in the bottle, the gel drops become

viscous once instilled into the eye, thereby

adhering better to the ocular surface and

ensuring hydration and protection.

In our study, Waterfall tear replacement was

instilled 3 times daily, instructing patients to

keep the eyes closed for about 20 seconds

after instillation so as to improve patient

acceptability. The corneal residence time of

an artificial tear plays an important role in

terms of protection, symptom relief and also

compliance. The innovative aspect of Water-

fall gel is its ability to become a gel after be-

ing instilled into the eye, thereby ensuring

long-lasting hydration and protection of the

ocular surface. Particular attention was paid

to the method of instillation, the number of

instillations and the constancy of treatment

over the 90 days of the study. The eye drops

were provided to all patients by our center.

All the patients were particularly motivated

owing to their clinical situation and attend-

ed all of the scheduled follow-up appoint-

ments without exception, allowing for a pre-

cise and thorough evaluation of the results.

Figure 3. Quality of Life: 67% of patients reported a marked subjective improvement in symptoms and quality of life, whereas 33% reported only a relative improvement with no change in symp-toms compared with the beginning of the study.

Improved

Unchanged

67%

33%

6

In particular, there was an improvement in

scores on the OSDI questionnaire adminis-

tered to the patients at baseline and at the

end of the study, indicating a reduction in

the impact of ophthalmological discomfort

on the patients’ daily life (Figure 5).

Figure 5. Ocular Surface Disease Index (OSDI). The OSDI questionnaire was used to investigate the impact of symptoms on the patient’s daily life. The improvement of OSDI scores from baseline to study end indicates a lower impact of ocular symptoms on the patient’s daily life. The four patients with the best results are shown.

OSD

I tot

al s

core

0

10

20

45

Patient 2

15

4

23

11

39

13

9

1

Patient 3 Patient 4 Patient 7

40

30

5

15

35

25

1st visit

3rd visit

Figure 4. Break-Up Time (BUT) test. The BUT tests were performed using a SIRIUS corneal topographer without the use of fluorescein; the patient was asked to blink twice in a row and then to keep the eye open for as long as possible. Results show an overall objective improvement of the ophthalmological parameters with an increase in BUT test values. The three patients with the best results are shown.

1.2 1.2

4.3Brea

k-U

p Ti

me

(sec

)

0

4

8

18Patient 1

1st Visit

10.4

16.8

15.4

3rd Visit

10

14

2

6

16

12

Patient 2

Patient 3

Treatment with Waterfall artificial tears in patients with alterations and dysfunction of the corneaand lacrimal apparatus

7

Conclusions

Between September and December 2019,

Waterfall eye drops were used on a selection

of 11 patients affected by dry eye disease

and keratopathy. The response and tolerance

of the patients who used the hypotonic eye

drops and benefited from the instillation was

good, in terms of both subjectively reported

symptoms and objective improvement of the

corneal and tear film parameters. The eye

drops were well tolerated, with only some

initial discomfort after instillation and good

compliance with the treatment over the fol-

lowing weeks. From an ophthalmological

viewpoint, the use of Waterfall eye drops

produced a reduction of the patients’ dis-

comfort and symptoms, with an increase in

BUT test values and, to a lesser extent, in cell

density.

In summary, the use of Waterfall hypoton-

ic eye drops, which may be combined with

anti-hypertensive or anti-inflammatory

therapy, seems to allow an early qualitative

improvement of vision, with a reduction

of all symptoms related to conditions such

as tear-film dysfunction, keratopathy, and

corneal dystrophy. The ophthalmological

improvement results in a better quality of

life for the patients.

References1. Leibowitz HM. Malattie della cornea-Diagnosi clinica e trattamento. Roma: Verduci Edi-

tore, 1986.

2. Dry Eye Workshop Subcommittee. The definition and classification of dry eye disease:

report of the Definition and Classification Subcommittee of the International Dry Eye

WorkShop (2007). Ocul Surf 2007;5(2):75–92.

3. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report.

Ocul Surf 2017;15(3):276–83.

4. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the

International Dry Eye WorkShop (2007). Ocul Surf 2007;5(2):93–107.

5. Friedman NJ. Impact of dry eye disease and treatment on quality of life. Curr Opin Oph-

thalmol 2010;21(4):310–16.