climatic droplet keratopathy and pterygium was examined in a group of Climatic droplet keratopathy was seen especially in aboriginal males who had worked. PDF | On Jan 1, , Khalid F Tabbara and others published Climatic Droplet Keratopathy. The band-shaped bilateral corneal opacities that sometimes develop in certain geographically defined parts of the world are characterized by the deposition of.

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Climatic droplet keratopathy CDK is a degenerative corneal disease of unknown etiology. A deeper knowledge of CDK pathogenic mechanisms will provide new therapeutic strategies. For that reason we investigated the prevalence of CDK in El Cuy and its existence in other 3 provinces with similar climate.

Patients eyes were examined, habits throughout lives were inquired about, and serum ascorbate sAA was determined. All individuals work outdoors for most of the day. All regions had normal O 3 levels. Conversely, region 4 individuals had balanced diet and higher sAA concentrations. CDK was only found in region 3 where individuals had partial deficiency of sAA and did not use eye protection.

No CDK was found in regions 1 and 2 where individuals had similar work activities and dietary habits to those in region 3 but wear eye protection.

No disease was found in region 4 where individuals work outdoors, have balanced diet, and use eye protection. To summarize, the CDK existence was related not only to climate but also to the dietary habits and lack of protection from sunlight. InBaquis [ 1 ] described for the first time an acquired degenerative disease of the human cornea colloid degeneration of the corneapotentially disabling and being characterized by a slow progression to corneal driplet. The general clinical features of this disease, which occurs in individuals who inhabit certain arid regions of the world [ 2 — 5 ], were reported by Klintworth [ 6 ].

The first descriptions of the ddoplet were given by Baquis in [ 1 ] and also in by Lugli [ 7 ]. InZanettin found climatic droplet keratopathy CDK in fishermen from the Dahlak Archipelago of the Red Sea and described a severe form which leads to blindness [ 8 ]. Since then, the disease has been described in different parts of the world [ 9 — 33 ] and more recently in Argentina [ 34 ].

The severity of this disease can be classified in three stages, according to the portion of cornea involved and the clinical aspects: A prelimbal fringe of clear cornea is also frequently observed. At this stage, the visual acuity is not compromised. The indemnity of the superior cornea, protected by the eyelid, suggests an etiologic factor contributing to chronic corneal exposure to ultraviolet radiation UVR and other stresses. In advanced cases, areas of the anterior stroma with vascularization, opacification, or fibrosis may be seen.

In general, the visual acuity is severely affected by this stage. In addition to the findings related to the cornea, the solar radiation that chronically reaches the bottom and most exposed part of the iris could play an important role in inducing depigmentation or atrophy in superficial layers, as previously observed in some patients with CDK [ 35 ].

Although globular deposits in the anterior layer of the corneas with CDK were described many years ago using optical and electron microscopy [ 3637 ], more recently, these anomalies have been further characterized by us using in vivo confocal microscopy IVCM [ 38 ].

Although some components in the corneal droplets have been identified [ 3940 ], the exact composition still remains unknown. A few years ago, Fujii et al. Tears contain many identifiable proteins [ 45 ], with the variation in their composition possibly defining biomarkers that could lead to a better understanding of the underlying pathology [ 46 ]. As CDK is an ocular surface disease and the analysis of the tear proteins may result in further understanding of this disease we studied tears glycoproteins in CDK patients using glycopeptide capture techniques and proteomics.

Our results suggest that the enzymatic glycosylation may also be involved in the formation of deposits in CDK, since altered levels of N-glycosylation of certain proteins were observed in the tears of patients with CDK [ 47 ]. We have also investigated matrix metalloproteinases MMP and their inhibitors, TIMP, in patients with CDK, because these molecules control the degradation of the corneal epithelium and stroma.

We showed increased levels of gelatinases and proinflammatory cytokines, as well as decreased expression of TIMP-1 in tears and biopsies of patients with CDK. Similar results were obtained when corneal epithelial cells were exposed to UVR in vitro [ 4849 ]. This data suggests that the pathogenesis of this disease is partly driven by a significant inflammatory response with the poor antiproteolysis shield making the cornea more vulnerable to increased levels of MMP.

The present study was conducted in order to investigate if nutrition, work activity, and eye protection from solar radiation are involved in the development of CDK. We carried out this research by studying individuals who inhabit a region of Argentinean Patagonia where we have found patients with this corneal disease El Cuy department in the Argentinean Patagonia and in other three Argentinean regions with climatic conditions similar to those of El Cuy department.


Even though this disease has received different denominations over the years, CDK being the most common name, we shall try to convince the scientific community that, based upon the results of this paper, a more accurate name for this corneal pathology would be environmental droplet keratopathy, rather than climatic droplet keratopathy.

The soil is clayey-sandy and covered by low shrub or steppe vegetation. The region experiences hot dry summers often exceptionally hot and cold winters, with great diurnal temperature variations. It is protected from winds by the edges of the plateau, which act as walls. Nonprobabilistic consecutive patients older than twenty years, who live during their entire life in any of these regions of Argentina and who agreed to take part in the study after reading a summary of the research project and signed a written consent, were examined by specialists in ophthalmology.

The study sample was composed of 89, and individuals for regions 1, 2, 3, and 4, respectively. Many individuals also received a test of visual acuity with a Snellen chart and Landolt rings or E for illiterate individuals, objective refraction determination using an autorefractometer RK1, Canon Inc.

Three representative cases of patients with different grades of CDK were also studied using in vivo confocal laser scanning microscopy IVCM as previously described [ 38 ].

Climatic droplet keratopathy: an old disease in new clothes.

All patients completed a questionnaire related to diet, work activity, and the wear of eye protection sunglasses, hats during their entire life. For region 3 only CDK patients were studied. For each year, four measurements were obtained on March 21, June 21, September 21, keratpoathy December 21 in order to determine the annual average.

The data were analyzed using different statistical tests such as Chi-Square test and analysis of variance ANOVA followed by post hoc least significance difference.

The level of statistical significance was set at. Table 1 presents the data for the average age, gender distribution, and prevalence of CDK in individuals living in the four Argentinean regions. No cases were kfratopathy in individuals younger than 38 years old.

In Figure 2IVCM oblique images of three representative patients with meratopathy grades of the disease clearly show the increase in hyperreflective dot-like deposits at the subepithelial layer as the disease progress. Values of pterygium and pinguecula are summarized in Table 2.

Pinguecula prevalence was significantly higher than pterygium for regions 1, 2, and 3, but not for region 4. When we compared the prevalence of pterygium among cclimatic four regions there was no significant differencewhereas the prevalence of pinguecula was of significant difference.

In the same region where we found CDK there was the highest prevalence of the other two diseases. The pterygium and pinguecula prevalence were significantly higher in region 3, only when they were compared keratoppathy values from region 4 andresp. The principal labor activities for the different regions are summarized in Table 3. The occupation in region 1 is sheep and domestic camelid breeding, whereas for region 2 it is goat rearing, logging, and coal dropoet. Individuals in region 3 clumatic mainly dedicated to sheep farming, sheep shearing, and, in some cases, the manufacture of wool, while individuals in region 4 work on tasks related to the cultivation, harvesting, and packaging of pears, apples, and dropleet.

The main dietary habits of individuals in region 1 are the consumption of meat, quinoa, corn, and potatoes; in region 3 sheep meat is ingested two or three times a day, with small amounts of milk taken sporadically.

Vegetables and fruit are exception items in the diet of the inhabitants of these regions. The diet of individuals in region 2 consists of some vegetables potatoes, zucchinisome meat, and a scarce amount of fruits.

In contrast, individuals inhabiting region 4 have a balanced diet meat, vegetables, sroplet, and fruit Table 3. In all regions, individuals manifest drinking yerba mate infusion a local infusion.

Dietary deficiency in foods rich in AA ketatopathy reflected in the low sAA levels found ketatopathy the individuals living in regions 1, 2, and 3 0. These values differed significantly from individuals in region 4 0. The twenty-five CDK patients manifested they worked outdoors in sheep farming, never used eye protection, had a very restricted diet as previously shown during their life, and had the lowest AAs concentration.

As can be seen in Keratopatgy 3 the majority of individuals from this region who do not suffer CDK have the same work activity and habits. When the total O 3 column concentrations Dobson units measured on March 21, June 21, September 21, and December 21 of each of the last ten years from each region were analyzed no significant differences at annual average were found data not shown. These results rule out any thinning of the ozone layer in the four studied regions.


CDK has been defined as a rural disease in which the clinical presentation and severity of corneal injuries can vary significantly depending on the region and its weather. More severe forms of CDK have been described in arid regions with high temperatures, such as those of the islands of the Red Sea [ 829 ], than in cold regions such as Labrador and the Arctic Circle climativ 23 ].

The combined use of slit lamp biomicroscopy and IVCM facilitate the diagnosis of this disease [ 3538 ]. We have recently shown elsewhere that, in patients with CDK, a hypersensitive reaction occurred in the cornea with the initial participation of important proinflammatory components of the innate immune system [ 52 ].

Climatic Droplet Keratopathy: II. Pathologic Findings | JAMA Ophthalmology | JAMA Network

We have previously shown a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Argentina [ 53 ]. Also, in previous unpublished studies we have investigated the variation at the blood and HLA-DRB1 alleles groups between patients and relevant controls. Although the eye depends on the energy from visible radiation to carry out its fundamental physiological processes, it can also be damaged by this radiation as well as by UVR.

Eye diseases in which sunlight is implicated are called ophthalmoheliosis, with these conditions representing important eye health hazards in many communities worldwide.

Spheroidal Degeneration

However, the interpretation of clinical examination is complicated, because of the difficulty in measuring the quantity and exact wavelength of light to which dropelt individual has been exposed, as well as the length of time over which an injury has been progressing [ 54 ].

Acute or chronic corneal exposure to UVR induces altered proteins, DNA fragmentation, free radical generation, lipid peroxidation, and so forth, resulting in actinic keratosis or keratopathies affecting primarily the epithelium and the anterior stroma.

Other studies have shown that exposure to UVR is responsible for the development of cortical pterygium and cataracts [ 55 ]. This vitamin is synthesized by different mechanisms both in the animal kingdom and in plants.

Tears also have keratopzthy different components that prevent oxidative stress a constant level of AA which is maintained by the lachrymal gland and not by the cornea [ 5760 ]. Our group, as others, working with guinea pigs fed on different doses of AA and exposed to UVR, have shown that cornea damage produced by radiation is related to the dose of AA consumed [ 596162 ]. However, association does not necessarily mean causation. To infer causality, it is necessary to conduct field studies to assess the individual dose-response to UVR.

The values of UVR can be calculated at ground level using radiometers or computer programs that manipulate different variables such as ozone, latitude, date, time, and cloudiness, among others [ 66 ].

The estimation of UVR dose reaching the eyes is also very important in order to be able to determine its harmful effects. However, getting these values requires the installation of equipment with constant evaluation by qualified staffs, which have to simultaneously record climatic factors, such as clouds and winds. Given that CDK is a chronic disease of slow evolution, we should had made all these measurements for many consecutive years in the four extremely isolated Argentinean regions we investigated, which was certaintly an unfeasible task.

For these reasons, in the present investigation we did not calculate the UVR values at ground level for any of the four Argentinean regions. Instead, we determined the total Keratopatjy 3 column concentration for these regions during 10 years using the website of the National Aerospatial Agency NASA, USAand all the O 3 values found during this extended period of time were within the normal range, excluding the possibility of any thinning in the O 3 layer in these Argentinean regions which keratopatthy have increased the amount of UVR reaching the ground surface and affect the individuals corneas.

Our findings also allowed reaching conclusions about the role played by labor activity, diet, and the use of appropriate eyes protection on the genesis of CDK. We observed CDK only in people who worked in sheep farming during their entire life in region 3 of Argentina characterized by a dry, sunny climate, with sandy and arid soil sparsely covered by climahic shrubs that only allowed the development of highly adapted plant species, which could be exploited by cattle, but was not suitable for growing vegetables or fruits.

Surprisingly, we did not find CDK in region 1 or 2 provinces of Jujuy and Santiago del Ekratopathywhich had similar climate and soils and where individuals have similar eating habits and work activity to those of region 3. The questionnaire about food consumption clearly indicated a dietary deficiency of rich vitamins foods, especially AA, in individuals from regions 1, 2, and 3.

Those answers were corroborated by the low sAA concentrations found in blood samples.