david ciacci, francesca jonsson...the symptoms related to dysfunction of the lacrimal apparatus;...

Innovation in Ophthalmology

Puro Protect® eye ointment for the treatment of corneal

disorders and lacrimal dysfunctions

David Ciacci, Francesca Jonsson

Year XXIV, N. 11, July 2021

Year XXIV, n. 11, July 2021

Puro Protect® eye ointment for the treatment of corneal disorders and lacrimal dysfunctionsDavid Ciacci, Francesca Jonsson

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Contents

Abstract 2

Introduction 3

Patients and methods 4

Results 5

Conclusion 7

References 8

Puro Protect® eye ointment for the treatment of corneal disorders and lacrimal dysfunctions

David Ciacci1, Francesca Jonsson2

1 Head of Ophthalmology, Chiros Srl, Turin, Italy; Director of Ophthalmology Service, Cidimu Group SpA, Turin, Italy; IRR Rehabilitations Institute, Turin, Italy

2 Orthoptist and Ophthalmic Assistant, Chiros Srl, Turin, Italy; Ophthalmology Service, Cidimu Group SpA, Turin, Italy; IRR Rehabilitations Institute, Turin, Italy

2


AbstractThe aim of this study was to assess the effectiveness of an isotonic sterile ophthalmic ointment containing 0.4% sodium hyaluronate and vaseline (Puro Protect®*) in improving hydration and protecting the ocular surface and thus alleviating the symptoms of patients affected by lacrima-tion disorders or corneal alterations, providing relief and reducing the symptoms of dry eye and keratopathy.The study, which lasted 30-40 days, was conducted on a selection of 13 patients suffering from severe qualitative and quantitative lacrimation disorders, dry eye and corneal dysfunctions or alterations, such as corneal dystrophies, keratopathies, epitheliopathies and/or sequelae of cor-neal transplants. The patients underwent an ophthalmological examination at baseline and a follow-up examination after 30-40 days of treatment with the ophthalmic ointment (Puro Pro-tect®) to assess the subjective and objective benefits of the treatment by means of specific tests and questionnaires. The patients’ response to treatment with the ointment was good, with a marked improvement in the symptoms related to dysfunction of the lacrimal apparatus; tolerance was fair, as the prod-uct’s ointment formulation was reported to cause blurred vision, which created some difficulty for a few minutes after the application.

Keywords: corneal disorder, dry eye, lacrimal dysfunction, ophthalmic ointment

Abbreviations: OSDI (Ocular Surface Disease Index), TFBUT (tear film break-up time)

*Puro Protect® is also known as Protectorial®


3

INTRODUCTION

Dry eye is an ocular disorder caused by hy-

polacrimia, excessive tear evaporation or

altered quality and composition of the tear

film1,2.

In Italy, dry eye affects 25% of the adult

population, mostly women older than 45

years. Dry eye syndrome can be prima-

ry or secondary: the secondary form can

result from systemic diseases, especially

those involving the immune system (sys-

temic lupus erythematosus, rheumatoid

arthritis, Sjögren’s syndrome, etc.) or be

caused by hormone changes (menopause,

pregnancy, etc.).

In predisposed subjects, pollution or pro-

longed exposure to video display terminals,

typical of today’s working conditions, can

worsen ocular dryness and favor the de-

velopment of a more severe form of dry eye

syndrome.

Excessive tear evaporation is also caused by

inflammatory states of the ocular adnexa,

such as conjunctivitis or blepharitis, as well

as by misuse or overuse of contact lenses,

long-term use of topical agents (e.g., pres-

sure-lowering eye drops in glaucoma) and

systemic medications (hormones, immuno-

suppressants, antihistamines, antidepres-

sants, etc.), or be a sequela of surgical pro-

cedures (e.g., photorefractive keratectomy,

phakorefractive surgery, cataract surgery)2

(Figures 1 and 2).

The main symptoms reported by the pa-

tients are vague and nonspecific ocular

disturbances, with eye pain, foreign body

sensation, redness, burning, visual cloud-

ing, and photophobia. Paranasal symptoms

Figure 1. Paracentral corneal dystrophy in a pa-tient with dry eye.

Figure 2. Patients with dry eye and marked conjunctival hyperemia.

4

similar to those experienced in seasonal al-

lergies may often be associated.

Ophthalmological assessment involves tak-

ing an accurate ophthalmological history to

elicit the patient’s symptoms, carrying out a

thorough eye examination with the use of

slit-lamp biomicroscopy to detect the objec-

tive signs of dry eye and, finally, perform-

ing diagnostic tests such as the tear film

break-up time (TFBUT) test, the Schirmer

test, meibography, and a tear osmolari-

ty test to determine the extent of dry eye

and the severity of the patient’s symptoms2.

Based on the results, the ophthalmologist

can then prescribe the most appropriate

treatment.

The present study aimed to evaluate wheth-

er treatment with a new ophthalmic oint-

ment (Puro Protect®) could improve the

subjective symptoms and visual well-being

of patients affected by corneal dysfunction

or alterations of the lacrimal apparatus, and

whether the possible benefit was substan-

tiated by an objective improvement in the

ocular parameters measured by diagnostic

tests and ophthalmological examination.

PATIENTS AND METHODS

The study involved 13 patients suffer-

ing from congenital or acquired corneal

disorders (cornea guttata, keratopathies,

epitheliopathies, corneal dystrophies)

(Figures 3 and 4) and lacrimal alterations

with severe subjective symptoms. The

sample was selected from among a larger

patient population that was assessed and

interviewed to exclude those affected by

pathological conditions that might reduce

homogeneity of the cohort and special cases

that could interfere with the study results.

Patients were assessed at baseline and af-

ter 30-40 days of treatment. The parameters

assessed included: ophthalmological exam-

ination, a TFBUT test, endothelial cell count,

Schirmer test, score on the OSDI (Ocular

Surface Disease Index) questionnaire;3,4 addi-

Figure 3. Mild epitheliopathy in a patient with poor lacrimation.

Figure 4. Patient with dry eye with previous corne-al lesions, mild corneal edema and poor lacrimation.


5

tionally, at 30-40 days patients were admin-

istered an individual questionnaire investi-

gating patient satisfaction with the ointment.

The study lasted a total of 30-40 days

and involved two visits. At the first visit

(time 0), the patients underwent a complete

eye examination, TFBUT test, endothelial

cell count, Schirmer test and OSDI assess-

ment. At the second visit (time 0 + 30-40

days), in addition to the eye examination,

TFBUT test, endothelial cell count, Schirm-

er test and OSDI assessment, the patients

were also interviewed to assess treatment

adherence, tolerance and correct use of the

ointment, and were invited to complete a

patient-satisfaction questionnaire.

The TFBUT test, used to measure the time

taken for an interruption in the tear film to

become visible on the corneal surface, was

performed with a SIRIUS instrument with-

out the use of fluorescein; patients were

asked to blink twice and then keep the eyes

open as long as possible.

The Schirmer test, which quantifies tear pro-

duction, was carried out by placing sterile

filter-paper strips, calibrated in millimeters,

into the patients’ lower conjunctival fornices.

The endothelial cell count was performed

with a no-contact instrument and used to

study the structure of the corneal endothe-

lium by analysing cell density, polymegath-

ism and pleomorphism.

Patients were invited to complete the OSDI

questionnaire, which investigates the extent to

which the reported symptoms affect daily life.

The new product, Puro Protect®, is an iso-

tonic ophthalmic ointment that contains

0.4% sodium hyaluronate. The ointment

formulation favors the product’s persistence

on the ocular surface and, combined with

sodium hyaluronate, it forms a film on the

ocular surface guaranteeing protection and

hydration of the eye. The patients were in-

structed to apply the ointment at bedtime

(though some patients applied it in the

morning owing to personal preference),

and were advised to hold the tube under

hot running water before use as this would

make the product more fluid and easier to

apply; the product was to be used along

with the other treatments prescribed for

corneal alteration and lacrimal dysfunction.

The importance of applying the product

correctly and constantly during the study

period was emphasised. All patients were

issued with the ophthalmic ointment.

RESULTS

The patients selected for the study were

13 and the study period lasted 30-40 days.

Owing to their symptoms, all patients were

strongly motivated and willing to use the

ointment and attend the scheduled fol-

low-up visit, allowing the study objectives

and results to be achieved. The study ex-

cluded those patients who were unable to

carry out the treatment constantly or who

independently discontinued it for any rea-

son, even half way through the planned

study period.

The 13 patients who completed the study all

used the ointment correctly, never skipped a

6

daily application, and regularly attended the

follow-up visit as per schedule.

The results of the patient-satisfaction ques-

tionnaire indicated a general subjective im-

provement perceived by all the patients, with

good compliance and fair tolerance. Consis-

tent with published data5, the patients re-

ported that their eye disturbances and qual-

ity of life had improved after only a few days

of use, and some of them expressed their in-

tention to continue using the product even

after the end of the 40-day study period. In

detail, 9 of out 13 patients reported a con-

siderable improvement in their ocular symp-

toms and disturbances, whereas 4 reported

no change following use of the ointment.

As for the instrumental and diagnostic tests,

the endothelial cell count did not reveal any

evident change or improvement, most like-

ly because the study duration (40 days) was

too short to detect any appreciable change

in this diagnostic parameter. The mean val-

ues of the endothelial cell counts at baseline

showed diffuse epitheliopathies with dif-

fuse polymegathisms and pleomorphisms,

findings that were essentially unvaried after

treatment with the ointment.

Most patients, on the other hand, showed a

marked improvement on the Schirmer test,

with tear production increasing between

46.6% and 78.3% (Figure 5), and on the

TFBUT test, with an increase in break-up

time between 38.5% and 48.3% (Figure 6).

The results of the OSDI questionnaires ad-

ministered at baseline and at study end also

improved, with the patients’ scores decreas-

ing between 32.4% and 57.5% (Figure 7),

indicating less ocular discomfort experi-

enced during daily activities. The results of

the final questionnaire investigating the tol-

erance and benefits of the use of Puro Pro-

tect® ointment were also positive.

Figure 5. Schirmer test performed at study start (baseline) and study end after 30-40 days of treatment (follow-up visit), considering separately the patients with dry eye disease (DED), cornea guttata or keratopathy.

Tear

�lm

pro

duct

ion

(mm

)

12

10

8

6

2

4

0DED

+46.6%+78.3%

+61.8%

Cornea guttata Keratopathy

Baseline Follow-up visit


7

CONCLUSION

The ointment was used over a period of 30-

40 days by a selection of 13 patients who

presented with lacrimal dysfunction and

corneal alterations.

Figure 6. TFBUT test performed at study start (baseline) and study end after 30-40 days of treatment (follow-up visit), considering separately the patients with dry eye disease (DED), cornea guttata or keratopathy.

Figure 7. OSDI questionnaire administered at study start (baseline) and study end after 30-40 days (follow-up visit), considering separately the patients with baseline OSDI scores >30, 20-30, <20.

TFB

UT

(sec

)

12

10

8

6

2

4

0DED

+48.3%

+46.3%

+38.5%

Cornea guttata Keratopathy


OSD

I

40

35

30

25

15

10

5

20

0OSDI >30

–32.4%

–57.5%

–33.7%

OSDI between 20-30 OSDI <20


8

The patients’ subjective response to the

ointment was excellent with reports of both

immediate relief after the first application

and sustained relief lasting a long time after

application. The patients reported perceiv-

ing less ocular dryness on getting up in the

morning and they described in great detail

the improvements experienced in visual

quality.

Tolerance of the ointment was fairly good,

with patients reporting some difficulty ap-

plying it and handling it; despite these small

inconveniences the patients showed good

compliance in using the product daily over

the weeks following the first application

and throughout the 30-40 days of the study

period.

It should be noted that the initial patient

cohort was larger but we excluded a certain

number of patients who reported having

difficulty applying the ointment and not

tolerating it for several hours following ap-

plication, which made them unable to con-

tinue the treatment for the planned 40 days.

In the patients who showed a good response

to the product, who were better selected

from an ophthalmological point of view, use

of the ointment improved ocular discomfort

and symptoms, and the ophthalmological

assessments at 30-40 days revealed a reduc-

tion of the previously noted conjunctival in-

flammatory phenomena, with less conjunc-

tival hyperemia and a slight increase in the

tear meniscus.

The majority of patients reported qualitative

and quantitative improvements with reduc-

tion of symptoms, increased hydration and

subjective relief; only a small proportion re-

ported no change with use of the ointment.

To conclude, the application of this oph-

thalmic ointment, which can be used in

combination with other pharmacological

treatments, seems to improve the quality

of the tear film, as demonstrated by the in-

creased TFBUT parameters, as well as the

quantity of tears produced, as shown by the

Schirmer test results. Both of these positive

effects reduced the patients’ discomfort and

improved all of their subjective symptoms

related to lacrimal dysfunction, keratopathy

or corneal dystrophy, ultimately improving

their individual quality of life.

References1. 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):75-92.2. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul

Surf 2017;15(3):276-283.3. Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II Diagnostic Methodology Report. Ocul

Surf 2017;15(3):539-574.4. Guarnieri A, Carnero E, Bleau AM, et al. Relationship between OSDI questionnaire and ocular

surface changes in glaucomatous patients. Int Ophthalmol 2020;40(3):741-751.5. Friedman NJ. Impact of dry eye disease and treatment on quality of life. Curr Opin Ophthalmol

2010;21(4):310-316.

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