The aim of this mini review is to describe the prevalence of Environmental Proteinaceous Corneal Degeneration (EPCD), pinguecula and pterygium and the association among them. We performed a transversal/observational study in individuals living all their lives in the El Cuy Department, province of Río Negro in the Argentinean Patagonia. The patients investigated were consecutive non-probabilistic. The prevalence of ophthalmoheliosis was 34% of pinguecula, followed by 30% of EPCD and 12% of pterygium. A statistically significant association was found between EPCD and male patients (p <0.05). There was association between EPCD with pinguecula and with pterygium, both more frequent in males (p <0.05). Our investigation shows important prevalence of EPCD, pinguecula and pterygium in individuals that live at this region of the Argentine Patagonia. As far as we know, this is the first work in the world that shows coexistences between these three ophthalmoheliosis.
Keywords: Environmental proteinaceous corneal degeneration; Pterygium; Pinguecula; Argentina
The term helioses derives from the Greek root “hēlíōsis” which means excessive exposure to sunlight, a mixture of radiation with wavelengths ranging from 200nm to 4000nm, which comprises Ultraviolet Radiation (UVR), visible light and infrared light . UVR has been found to reach diverse ocular components and is strongly absorbed by the anterior structures of the eye . The cornea absorbs UVR differentially, based on the incident wavelength. More than 90% of UVR-C and UVR-B are absorbed by this ocular structure, as well as 60% of UVR-A , while the rest of the UVR-A is absorbed by the crystalline, with less than 1% reaching the retina . Absorbed UVR is an important source of stress for the ocular surface through direct photo-oxidation (or type I). Also, indirect photo-oxidation (type II) can occur and produce Reactive Oxygen Species (ROS), which damage protein, lipids and cellular DNA [5-8].
There are different eye diseases associated with harmful exposure to UV light without adequate eye protection, known as ophthalmoheliosis. Among them, we can mention three degenerative diseases of the ocular surface: Climatic Droplet Keratopathy (CDK), pinguecula and pterygium. These diseases with still elusive etiology but with possibly multifactorial origin are frequently found in rural environments with high insolation. CDK is a rare acquired, bilateral degenerative disease of the cornea, which is highly prevalent in certain rural communities exposed to harsh weather conditions, that evolves through three
different degrees of severity, leading to severe visual compromise as the result of corneal opacification . As CDK is not specifically associated to weather, but to certain environmental conditions, we have proposed to name it Environmental Proteinaceous Degenerative of the Cornea” (EPCD) . Current revisions on advances of molecular mechanisms involved in EPCD and pterygium have been published by Serra  and by Cardenas-Cantu .
Pinguecula is a yellowish globular or flat benign conjunctival growth, near the corneal limbus in the interpalpebral fissure, produced by the alteration of the underlying connective tissue [13,14]. Although there is some evidence of its development upon exposure to sunlight , its pathogenesis is ignored. In some patients, it seems to be a precursor of a pterygium . Even though the prevalence of one or more of these distinct ophthalmoheliosis have been studied in different parts of the world, as far as we know the co-existence of these degenerative diseases of the ocular surface has not yet reported. The purpose of this mini review is to present the prevalence of EPCD, pinguecula and pterygium and associations among them, in individuals who lived their entirely life in the Argentinean Patagonia.
Our studies were approved by the Council for Ethical Research Evaluation of the government of the Province of Cordoba, Argentina, and registered in the Provincial Registry for Investigation in Health, Province of Cordoba. All studies
adhered to Helsinki declaration. The studies (non-probabilistic
consecutive, transversal / observational) were conducted in El
Cuy Department, Province of Río Negro, Argentina. In this area
of 11,281 km2, at 750 meters above sea level between 38º 56’
- 40º 25’ of south latitude and 67º 54’ - 69º 04’ west longitude.
According to the last census, 2,329 inhabitants live (1,311 males
and 1,018 women. It is worth to mention that the sample size for
this amount of population is equal to 71 individuals.
One hundred individuals (≥29 years of age), who have
lived their entire life in this region and agreed to participate
in this study signing an informed consent were examined by
ophthalmology specialist. All subjects underwent visual acuity
testing with Snellen chart, or Landolt/E rings for illiterate
individuals. Additionally, a detailed slit-lamp examination of the
anterior segment (conjunctiva, cornea, anterior camera and iris)
was done. Questions related to diet, work activity and the use of
eye protection (sunglasses, hats) during lifetime were asked to
As depicted in Figure 1, El Cuy Department is 280 km
from the border with Chile and 300km away from the Atlantic
Ocean. This region has a semi-arid weather (Bwk, Köppen
low shrubbery, annual rainfall lower than 190 mm, constant
strong winds, warm summers and cold winters, and great
thermal amplitude between day and night. The annual range of
temperature is between 4.6ºC and 18.2°C. Statistical studies of
value comparison was made using Pearson and ANOVA tests.
The level of statistical significance was set at p≤0.05.
All participants in the study had always lived in the area
previously described and there was no sex significant difference
in the population investigated (data not shown). Table 1 presents
the prevalence of pinguecula, EPCD, and pterygium, gender
distribution and mean age ± SD of the individuals studied. The
highest prevalence corresponded to pinguecula (34%), followed
by EPCD (30%) and pterygium (12%). A significant statistical
association was found between EPCD and patients’ sex (p≤0.05),
being it, more frequent in male (24%) than in female patients
(6%). However, no statistical differences were found between
pinguecula and pterygium when men and women were
compared, as well as between the ages of men and women for
any of the three diseases.
The mean ages were significantly different between patients
with versus without EPCD, but there was neither significant
difference in the mean age of patients with and without
pinguecula, nor in individuals affected or not with pterygium.
Fifteen out of thirty patients with EPCD presented only this
ophthalmoheliosis, 18 out of 34 patients with pinguecula had
this disease, and 5 out of 12 individuals with pterygium had this
degeneration of the ocular surface. Significant differences in the
association of EPCD with pinguecula and EPCD with pterygium
were found within the group of males (p≤0.05). Pinguecula
was more associated with EPCD than pterygium. Additionally,
there were small number of patients who simultaneously had
pinguecula and pterygium (Figure 2). We also analyzed the
clinical records of patients that only presented pinguecula, and
patients with pterygium at the time of the study, and we found
that they had all had these pathologies at least in the last 10
As regards lifestyle of the habitants of the studied region,
the main occupation of the population was breeding and
sheep shearing, and in some cases, wool processing and manufacturing. The main dietary habits of these individuals
included the ingestion of ovine meat two or three times a day
and small amounts of milk sporadically. Vegetables and fruit
were exceptional in their diet. Patients also manifested that they
drank mate infusion. As for eye protection, most did not wear
hats or sunglasses.
In this work we studied the prevalence of EPCD, pinguecula,
and pterygium, in a particular region of the Argentine Patagonian.
We found a high prevalence of EPCD (30%), coincidentally
with previous observations . Chronic inflammation and
microtrauma of the ocular surface by soil dust carried by
constant winds could be risk factors for EPCD. Additionally,
EPCD patients are exposed throughout life to UVR-B as they
work outside in that arid and shadeless region, not wearing eye
protection (sunglasses or hats). UVR-B is primarily absorbed
by means of electronic transitions of the peptides connection
(190-220nm) and by the aromatic motives of tryptophan,
tyrosine and phenylalanine (250-300nm) residue, which take
the partial folding and aggregation of proteins among which
there are enzymes such as Aldehyde Dehydrogenase (ALDH)
and glutathione peroxidase, which play an important role to
control oxidative stress . As EPCD patients have a partial
deficiency of ascorbate (AA)  (an important antioxidant
in the cornea) there is less absorption of UVR-B by the AA and
greater generation of ROS. These free radicals start a chain
reaction that results in the oxidation of poly-unsaturated lipid of
the cell membranes (lipid peroxidation) with its quantitative and
qualitative lipid alterations and generation of toxic and reactive
aldehydes . These molecules, in contrast to ROS, have a long
life and induce more protein aggregates, which characterize the
progressive corneal opacification in patients with EPCD .
Pinguecula was the most frequently found ophthalmoheliosis
in this study (34%). Most population studies in different parts of
the world show its prevalence ranging from 11.3% to 90% of
the adult population [20,21]. Pinguecula has been considered by
some as the precursor or trigger of pterygium . However, in
our study none evolved into pterygium in the 10-year follow-up.
Prevalence rates of pterygium in different population studies vary
from 0.7% to 60%, depending on the latitude and altitude of the
region where they are studied. Permanent exposure to sunlight
(UVR-B) close to the Equator is considered as the principal causal
factor of pterygium. However, low preponderances have been
reported in Beijing (3%), intermediate values (around 12%) in
Hawaii. Although pterygium has been reported as scant in the
north and south of parallels 40, there is a description of 5.9%
pterygium prevalence in a community at 42 degrees latitude N of
Spain. The prevalence of this disease around the world has been
recently reviewed by Rezvan . Our work shows a pterygium
prevalence of 12% in a population located at the north west of
Argentine Patagonia steppe (between 38º 56’ - 40º 25’ of south
All these findings indicated that, although exposure to UVR-B
could be a causal principal factor, it is far from being the only
one. There are works that document the existence of pterygium
related to certain ethnic groups (genetic predisposition) [23-
25], viral infections , and to defects in genes associated with
DNA repair . DNA is one of the greatest targets of UVR-B
induced oxidative stress, and the modified DNA can result in
genetic mutations . There is consensus that UVR-B causes
limbal focal defects, which are the main pathogenic factors in
Our investigations show the existence of EPCD, pinguecula
and pterygium south of parallel 30, outside the “pterygium
belt” described by Cameron . We found a greater number
and degree of EPCD severity in older men, but no difference
in the prevalence of pinguecula and pterygium between men
and women or between ages. As far as we know, this is the first
study that evaluates the coexistence of these three degenerative
diseases of the ocular surface.
Besides the individuals who only suffer from EPCD, or
pinguecula, or pterygium, we identified patients with EPCD and
pinguecula, others with EPCD and pterygium, a small number of
individuals with pinguecula and pterygium and individuals with
the three pathologies.
Even though there is a small cohort of pinguecula patients,
the follow up of these patients for ten years showed that it is
unlikely that pinguecula could be the beginning of pterygium.
These diseases of the ocular surface can cause ocular discomfort,
irritation, visual disturbance, and have cosmetic effects. They
can also cause frustration in the affected individuals, given that there is no medical treatment available. Pinguecula is
generally not treated, except for those cases which present
recurrent inflammation, while the treatments of advanced cases
of pterygium and EPCD, although they are different, consist of
the extraction of the affected areas by surgery. As have been
reviewed by Serra , different pterygium surgery techniques
have been developed in the last decade. In cases of marked
corneal opacity of patients with EPCD, penetrating or laminar
queratosplasty, and the implant of an amniotic membrane have
been used .
A greater knowledge of the genesis of these pathologies might
contribute to preventing such potentially disabling diseases,
taking into consideration that the cure is very complicated in
marginal zones of the planet where there is high prevalence. Our
investigations showed important prevalence of EPCD, pinguecula
and pterygium in individuals that live in a semi-deserted region
of the Argentine Patagonia, and coexistence of those diseases in
many of them.
Serra HM, Suarez MF, Esposito E, Urrets ZavalıaJ A (2014) Vitamin C functions in the cornea: Ultra-structural features in ascorbate deficiency. In: Preedy VR (Edition). The handbook of nutrition, diet and the eye. London, UK: Elsevier Inc Chapter 31: 311-320.