Climatic Droplet Keratopathy Research Articles

Integrated analysis of microRNA expression in tears of Kazakh patients with climatic droplet keratopathy in Xinjiang, China

Climatic droplet keratopathy (CDK) is a corneal diseases, which is characterized by increased oil-like deposits on the anterior elastic lamina and anterior stromal layer. Severe CDK can even cause blindness, with no specific available treatment. Besides. CDK is poorly understood in terms of its pathogenic mechanisms. Thus, to determine potential biomarkers for CDK, we analyzed the microRNA expression profile in tear samples from CDK patients and investigated their putative roles in the pathogenesis of CDK. Herein, miRNA sequencing and following bioinformatics analysis was performed to explore the roles of their target genes in CDK. A total of 67 differentially expressed miRNAs were identified, of which 25 were upregulated and 42 were downregulated. qPCR verification showed that among the up- and down-regulated miRNAs, expression of five and six, respectively, was most significantly different.The target genes of the differentially expressed miRNAs are involved in the FoxO signaling pathway, tumor necrosis factor (TNF) signaling pathway, and steroid hormone biosynthesis. Protein–protein interaction network analyses identified 20 hub genes, including PTEN, GSK3B, and SMAD3. In conclusion, the panel of differentially expressed miRNAs identified may have potential utility as early diagnostic biomarkers for CDK. Moreover, the TNF signaling pathway is a new potential target in CDK for the development of treatments.

MiR-1273h-5p protects the human corneal epithelium against UVR-induced oxidative stress and apoptosis: Role of miR-1273h-5p in climatic droplet keratopathy

Climatic droplet keratopathy (CDK) is characterized by an increased number of oil-like deposits on the most anterior corneal layers, which affect vision and can cause blindness. Environmental ultraviolet radiation (UVR) exposure is a major risk factor, but the underlying mechanism of CDK pathogenesis is unclear. Increasing evidence has demonstrated that miRNAs participate in the cross-talk with oxidative stress. We aimed to explore whether certain miRNAs are involved in the pathogenesis of CDK. We performed miRNA sequencing of tears from patients with CDK and healthy individuals from Tacheng region of Xinjiang and conducted bioinformatic analysis of key miRNAs. We also evaluated viability, migration, and apoptosis of human corneal epithelial cells (HCECs) subjected to UVR treatment. miR-1273h-5p expression was abnormally downregulated in the tears of patients with CDK. miR-1273h-5p promoted cell proliferation and migration and inhibited UVR-induced mitochondrial apoptosis. miR-1273h-5p protected HCECs against UVR-induced oxidative damage by reducing the accumulation of reactive oxygen species and inhibiting mitochondrial apoptosis via the activation of the Nrf2 pathway. Thus, our results suggest that miR-1273h-5p protects the corneal epithelium against UVR-induced oxidative stress damage.

Prevalence and associated factors for climatic droplet keratopathy in Kazakhs adults: a cross-sectional study in Tacheng, Xinjiang, China

BackgroundInvestigation of the prevalence of climatic droplet keratopathy (CDK) in Tacheng, Xinjiang, China.MethodsA total of 1030 participants, in their 40s or older, from the Kazakh ethnic group in Tacheng, were randomly sampled by stratification method. Ophthalmic examinations and surveys were carried out on these participants. Factors associated with CDK were analyzed with logistic regression models.ResultsCDK was found in 66 (6.4%; 95% confidence interval [CI]: 4.9–7.9%) Kazakh individuals.After multiple regression model analysis, it demonstrated that age (< 0.001), exposure time (< 0.001), exposure protection (< 0.001), and vegetable intake (< 0.001) were of correlation with CDK, of which age (OR = 1.21[CI]: 1.16–1.27) and long-term outdoor exposure (OR = 2.42[CI]: 1.26–4.67) were the risk factors, and that vegetable intake (OR = 0.29[CI]: 0.14–0.59) and wearing a hat (OR = 0.24[CI]: 0.10–0.56) were protective factors.ConclusionsThis study has revealed the risk and protective factors of CDK, providing a new insight on related research.

Pathological Changes of the Anterior Lens Capsule.

The anterior lens capsule (ALC), as the thickest basement membrane in the body, is an acellular, soft, smooth, transparent membrane secreted by lens epithelial cells. The ALC has its unique biomechanical properties to serve as a barrier and separate the lens from infectious viruses and bacteria together with the posterior capsule and pericapsular membrane. However, the biomechanical and ultrastructural properties of the ALC can be changed under certain conditions. Here, we provide a brief review of the pathological changes of the ALC in several eye disorders, including cataract, aniridia, climatic droplet keratopathy, exfoliation syndrome, true exfoliation syndrome, Alport syndrome, and silicone oil tamponade.

Case report of a ‘relatively’ new corneal disease

Peripheral hypertrophic sub-epithelial corneal degeneration was first described in 2003 and involves bilateral, symmetrical, peripheral, hypertrophic and sub-epithelial corneal opacification. The disease affects mostly young white women with light-coloured eyes and must be differentiated from corneal intraepithelial neoplasia, bullous keratopathy, climatic droplet keratopathy, corneal amyloidosis, corneal keloid, hereditary hypertrophic scarring, pseudo-pterygia and Salzmann’s nodular degeneration. This case report serves to highlight the clinical findings.

Adverse effect of UV radiation on eyes — a review

The aim of this study is to discuss the association between ultraviolet radiation (UVR) and eye diseases. UVR which reaches the surface of the Earth consists of 95% UVA and 5% of UVB. Both acute and chronic exposure to UVR leads to pathological changes in the eye. There is strong evidence that UVR exposure causes photokeratitis, photoretinitis, climatic droplet keratopathy, cataract, pterygium, squamous cell carcinoma of cornea and conjunctiva, cancer of the eyelids (squamous cell and basal cell carcinoma). Association between UVR and pinguecula, AMD (age-related macular degeneration) and melanoma of the eyeball is ambiguous. UVR exposure occurs all day and all year long, which is why eye protection is necessary to avoid diseases induced by UVR. In particular childrens’ eyes should be protected from the sun. Efficient protection is provided by accurate clothing, hats, eyeglasses or contact lenses blocking UV light.

Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy.

Climatic droplet keratopathy (CDK) is an acquired degenerative disease predominantly affecting males over 40 years old. It results in progressive corneal opacities usually affecting both eyes. CDK is multifactorial and its etiology remains unknown. Our recent findings are consistent with CDK pathology being driven by environmental factors with oxidative stress playing an important role (e.g.,, contributing to lipid peroxidation) rather than climate factors. The changes in corneal lipid composition affected by environmental factors remain understudied. The purpose of this study was to systematically investigate phospholipids profile (phosphatidylcholine [PC] and phosphatidylserine [PS]) in corneas from CDK patients using tandem mass spectrometry. Samples from CDK areas and from non-affected areas were obtained from patients diagnosed with CDK who underwent cataract surgery, were subjected to lipid extraction using a modified Bligh and Dyer method; protein concentrations were determined using the Bradford's method. Lipids were identified and subjected to ratiometric quantification using TSQ Quantum Access Max triple quadrupole mass spectrometer, using appropriate class specific lipid standards. All phospholipid classes showed lower total amounts in affected areas compared to control areas from CDK's corneas. Comparative profiles of two phospholipid classes (PC, PS) between CDK areas and control areas showed several common species between them. We also found a few unique lipids that were absent in CDK areas compared to controls and vice versa. Lower amount of phospholipids in CDK areas compared to control areas could be attributed to the lipid peroxidation in the affected corneal regions as a consequence of increased oxidative stress. J. Cell. Biochem. 118: 3920-3931, 2017. © 2017 Wiley Periodicals, Inc.

Damaging Effects of Ultraviolet Radiation on the Cornea.

The cornea sits at the anterior aspect of the eye and, like the skin, is highly exposed to ultraviolet radiation (UVR). The cornea blocks a significant proportion of UVB from reaching the posterior structures of the eye. However, UVA can penetrate the full thickness of the cornea, even reaching the anterior portion of the lens. Epidemiological data indicate that UVR is a contributing factor for a multitude of diseases of the cornea including pterygium, photokeratitis, climatic droplet keratopathy and ocular surface squamous neoplasia (OSSN), although the pathogenic mechanisms of each require further elucidation. UVR is a well-known genotoxic agent, and its effects have been well characterized in organs such as the skin. However, we are only beginning to identify its effects on the cornea, such as the UVR signature C → T and CC → TT transversions identified by sequencing and increased proliferative and shedding rates in response to UVR exposure. Alarmingly, a single low-dose exposure of UVR to the cornea is sufficient to elicit genetic, molecular and cellular changes, supporting the consideration of using protective measures, such as wearing sunglasses when outdoors. The aim of this review was to describe the adverse effects of UVR on the cornea.

Association of Pseudoexfoliation (PXF) with Glaucoma and Climate Droplet Keratopathy (CDK)

Purpose: To find out correlation of Pseudoexfoliation (PXF) with glaucoma and Climatic droplet keratopathy (CDK). Setting: Department of Ophthalmology, Sankara Eye Hospital, Krishnankovil, Tamil Nadu. Study design: An observational clinical study Patients and Methods: 50 patients with Pseudoexfoliation (PXF) and 50 patients without Pseudoexfoliation (PXF) were studied and analyzed for glaucoma and Climatic Droplet keratopathy (CDK). Results: PXF is strongly associated with glaucoma and significantly associated with Climatic Droplet Keratopathy.

Corneal changes in Pseudoexfoliative eyes

Aim: To look for corneal changes in Pseudoexfoliative eyes and its resulting clinical implication. Methods: This prospective study carried out at JSS Hospital, Mysore consisted of 100 consecutive patients with Pseudoexfoliation who presented to the outpatient department between January 2015 to December 2015. A detailed Ocular evaluation was done. Corneal changes were noted. Central corneal thickness was measured using ultrasound pachymetry Results: Male to Female ratio was nearly 3:2. 20 patients had pterygium in one or both eyes. The mean tear film break up time was 13.85 seconds. Mean Central corneal thickness in Pseudoexfoliation with glaucoma eyes (502.7± 12.82 µ) was found to be lower when compared with Mean Central corneal thickness in Pseudoexfoliation without glaucoma eyes (518.36±13.21 µ) and this was found to be statistically significant . Conclusion: Climatically induced changes like pterygium, climatic droplet keratopathy are seen in Pseudoexfoliative eyes probably due to common etiology. Evaluation of central corneal thickness is necessary in all patients with Pseudoexfoliative glaucoma due to thinner cornea and the risk of underestimation of intra ocular pressure.

A Study of Risk Factors for Climatic Droplet Keratopathy in Elderly Persons from Western Rajasthan

Climatic Droplet Keratopathy is an acquired degeneration of cornea. It is characterised by the deposition of amber coloured oily spherules at and around the Bowman's membrane of the cornea. The disease occurs in areas where exposure to ultraviolet (UV) light is excessive. Climatic droplet Keratopathy is a common ocular morbidity in this part of country. Intense sunshine, excess UV radiation, micro trauma due to wind borne particles, extremes of high or low temperature, aridity, malnutrition and genetic factors were incriminated as the etiological factors for the development of Climatic Droplet Keratopathy. We studied about the relation of Climatic Droplet Keratopathy to age, sex, laterality, familial pattern and working hours in sunlight. Climatic droplet keratopathy may be prevented by wearing UV blocking sunglasses in areas of sand and dust. Side protectors of the sunglasses may have to be placed to prevent exposure to environmental irritants. Keywords Climatic droplet keratopathy, Corneal Degeneration

Climatic droplet keratopathy: an old disease in new clothes.

Climatic droplet keratopathy (CDK) is an acquired and potentially handicapping cornea degenerative disease that is highly prevalent in certain rural communities around the world. It predominantly affects males over their forties. It has many other names such as Bietti's band-shaped nodular dystrophy, Labrador keratopathy, spheroidal degeneration, chronic actinic keratopathy, oil droplet degeneration, elastoid degeneration and keratinoid corneal degeneration. CDK is characterized by the haziness and opalescence of the cornea's most anterior layers which go through three stages with increasing severity. Globular deposits of different sizes may be histopathologically observed under the corneal epithelium by means of light and electron microscopy. The coalescence and increased volume of these spherules may cause the disruption of Bowman's membrane and the elevation and thinning of the corneal epithelium. The exact aetiology and pathogenesis of CDK are unknown, but they are possibly multifactorial. The only treatment in CDK advanced cases is a corneal transplantation, which in different impoverished regions of the world is not an available option. Many years ago, the clinical and histological aspects of this disease were described in several articles. This review highlights new scientific evidence of the expanding knowledge on CDK's pathogenesis which will open the prospect for new therapeutic interventions.

Climatic Droplet Keratopathy in Argentina: Involvement of Environmental Agents in Its Genesis Which Would Open the Prospect for New Therapeutic Interventions.

Climatic droplet keratopathy (CDK) is a degenerative corneal disease of unknown etiology. We described CDK for the first time in Latin America in the Argentinean Patagonia (El Cuy). 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 O3 levels. Individuals from regions 1, 2, and 3 had very low consumption of vegetables/fruits and low sAA 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.

The Role of Ultraviolet Radiation in the Ocular System of Mammals

With decreasing levels of ozone in the atmosphere, we are being exposed to higher levels of ultraviolet radiation (UVR) than ever before. UVR carries higher energy than visible light, and its effects on tissues include DNA damage, gene mutations, immunosuppression, oxidative stress and inflammatory responses. In the eye, UVR is strongly associated with the development of basal and squamous cell carcinoma of the eyelid, pterygium, photokeratitis, climatic droplet keratopathy, ocular surface squamous neoplasia, cataracts, and uveal melanoma, and is weakly associated with age-related macular degeneration. Despite overwhelming evidence regarding the deleterious effects on UVR, public health measures to encourage UV protection of the eyes is generally lacking. Options for photoprotection include sunglasses, wide brim hats, windshields, plastic films for side windows in cars, UV blocking contact lenses, and following the UV Index report daily. The American National Standards Institute currently has regulations regarding properties of UV blocking sunglasses; however, compliance in the US is not mandatory. On the other hand, UVR does have therapeutic applications in the eye, particularly, riboflavin activated by ultraviolet A light (UVA) radiation is used clinically to slow the progression of keratoconus, post-LASIK keratectasia, and bullous keratopathy by crosslinking corneal collagen fibers. Additionally, riboflavin activated by UVA has been shown to have antibacterial, antiviral, and antiparasitic effects. This is clinically relevant in the treatment of infectious keratitis. Finally, exposure to low levels of light in the UV spectrum has been found to regulate the growth of the eye and lack of adequate exposure may increase the risk of development and progression of myopia.

Ocular morbidity among refugees in Southwest Ethiopia.

Low vision and blindness are recognized as one of the major public health problems worldwide, especially in developing countries. The prevalence and cause of blindness and low vision vary from region to region, among different age and population groups in a country or geographical region. The objective of this study is thus to determine the causes of blindness and ocular morbidity among refugees in Southwest Ethiopia. A cross-sectional clinic based study was conducted on 1,054 refugees in Southwest Ethiopia. A basic anterior and posterior segment examination was done by ophthalmologists with Magnifying Loupe 2.5X and Direct Ophthalmoscope. Data were analyzed using SPSS version 16.0. The most common causes of ocular morbidity identified were trachoma 547(21.2%), cataract 501(19.4%), refractive error 353(13.7%), conjunctivitis 240(9.3%), glaucoma 130(5.1%) and climatic droplet keratopathy 112(4.4%). The overall prevalence of blindness was 26.2% and the prevalence of childhood blindness was 0.7%. The prevalence was higher among females (16.9%) than males (9.3%) and age groups 60 years and above (15.9%) than other age groups (10.3%) (P<0.05). The overall prevalence of low vision was 25.8% and the prevalence of low vision in pediatric age group was 0.9%. The leading causes of blindness were cataract 112(40.6%), trachomatous corneal opacity 58(21.0%) and glaucoma 49(17.8%). The commonest cause of low vision was cataract 102(37.6%) followed by trachomatous corneal opacity 49(18.1%) and refractive error 35(12.9%). There is a very high burden of blinding eye diseases among refugees. Integrated multidisciplinary intervention strategies for the prevention and control of blindness and low vision in the study settings should be initiated.

Exfoliation syndrome in sub-Saharan Africa.

The goal of this review is to estimate the burden of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in sub-Saharan Africa and to identify the gaps in knowledge of disease prevalence in this region. PubMed, Medline, African Journals Online and Google engine search were carried out using the following terms "pseudoexfoliation" or "exfoliation syndrome Africa", "pseudoexfoliation" or "exfoliation syndrome" + "glaucoma Africa," "glaucoma prevalence Africa," "pattern of glaucoma presentation Africa," "pseudoexfoliation" or "exfoliation syndrome" + "cataract Africa," "ophthalmic conditions Africa." Studies were included if they described the proportion or prevalence/incidence of XFG and XFS in sub-Saharan Africa or if they investigated lysyl oxidase-like 1 (LOXL1) variants in XFS among Africans. 22 papers were identified and classified as clinic-based studies (n = 16) and population-based (n = 4) studies. Two other studies were considered important, and therefore, included in the review. Clinic-based studies demonstrate that XFS is a common cause of glaucoma, as is true in many other parts of the world. Furthermore, XFS often co-exists with cataract and climatic droplet keratopathy. Its prevalence ranged from 5.1 to 7.7 % in patients >40 years in population-based studies, a value that is considerably higher than that reported in African Americans. XFS was strongly associated with increasing age in the prevalence studies. The burden of XFS in sub-Saharan Africa is high. More investigation is needed to determine why clinic-based studies report virtually no XFS in some countries (Ghana and Tanzania), while nearby countries report greater proportions (Nigeria and Ethiopia).

Genetic Background and Climatic Droplet Keratopathy Incidence in a Mapuche Population from Argentina

PurposeTo determine whether the incidence of and susceptibility to climatic droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal disease, is influenced by the genetic background of the individuals who exhibit the disorder.MethodsTo determine whether the disease expression was influenced by the genetic ancestry of CDK cases in native Mapuche of the northwest area of Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient) population, while 24 were part of the control group. The analysis revealed the maternal and paternal lineages that were present in the two study groups.ResultsThis analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. There was no significant difference in the frequencies of mtDNA haplogroups between the CDK patient and control groups. Although the Y-chromosome data revealed differences in specific haplogroup frequencies between these two groups, there was no statistically significant relationship between individual paternal genetic backgrounds and the incidence or stage of disease.ConclusionsThese results indicate a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears to play less of a role in CDK expression than for other complex diseases linked to bioenergetic processes. However, further analysis of the mtDNA genome sequence and other genes involved in corneal function may reveal the more precise role that mitochondria play in the expression of CDK.

In vivo confocal microscopy of climatic droplet keratopathy

We describe the corneal microstructural changes in a patient with spheroidal degeneration using in vivo confocal microscopy. Multiple hypo‐ and hyper‐reflective spherical lesions were observed in the anterior corneal stroma and Bowman's layer ranging from 45 to 220 μm in size. The corneal epithelium, posterior stroma and endothelium were otherwise unaffected. In vivo confocal microscopy demonstrates good correlation with excised histological samples in climatic droplet keratopathy. It provides a non‐invasive technique to examine the living cornea for degenerative disease and acts as a bridge between clinical and laboratory observations.

Ultraviolet light and ocular diseases

The objective of this study is to review the association between ultraviolet (UV) light and ocular diseases. The data are sourced from the literature search of Medline up to Nov 2012, and the extracted data from original articles, review papers, and book chapters were reviewed. There is a strong evidence that ultraviolet radiation (UVR) exposure is associated with the formation of eyelid malignancies [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)], photokeratitis, climatic droplet keratopathy (CDK), pterygium, and cortical cataract. However, the evidence of the association between UV exposure and development of pinguecula, nuclear and posterior subcapsular cataract, ocular surface squamous neoplasia (OSSN), and ocular melanoma remained limited. There is insufficient evidence to determine whether age-related macular degeneration (AMD) is related to UV exposure. It is now suggested that AMD is probably related to visible radiation especially blue light, rather than UV exposure. From the results, it was concluded that eyelid malignancies (BCC and SCC), photokeratitis, CDK, pterygium, and cortical cataract are strongly associated with UVR exposure. Evidence of the association between UV exposure and development of pinguecula, nuclear and posterior subcapsular cataract, OSSN, and ocular melanoma remained limited. There is insufficient evidence to determine whether AMD is related to UV exposure. Simple behaviural changes, appropriate clothing, wearing hats, and UV blocking spectacles, sunglasses or contact lens are effective measures for UV protection.

Pro-Inflammatory Cytokines and Gelatinases in Climatic Droplet Keratopathy

Climatic droplet keratopathy (CDK) is a degenerative disease of the cornea with possible involvement from matrix metalloproteinases (MMPs). Therefore, the authors investigated histologic distribution, levels, and molecular forms of MMP-2 and MMP-9, as well as tear fluid levels of MMPs and cytokines in CDK patients. They additionally examined UV-B-irradiation effect on production of gelatinases and cytokines by human corneal epithelial (HCE) cell culture model. Tears were collected from 20 unrelated individuals (10 with CDK and 10 controls). CDK affected corneas were haematoxylin-eosin stained and the presence and distribution of MMP-2 and MMP-9 was examined using immunohistochemistry. Gelatinases and cytokine secretion was measured in tears and supernatants from UV-B-exposed HCEs by immunoblotting, gelatin zymography, and protein array, respectively. MMP-2 and MMP-9 values were significantly higher in tears collected from CDK patients than healthy controls and were accompanied by pro-inflammatory cytokine secretion. Immunohistochemistry showed that MMP-2 was expressed at the basement membrane zone in both control and affected corneas, but also marked the edges of the granular CDK deposits; MMP-9 expression was restrained to basal layers of the epithelium and was markedly induced in CDK corneas. In HCE cells, UV-B increased gelatinase secretion, with a striking effect on MMP-9, and was preceded by pro-inflammatory cytokine release. The authors demonstrate that the corneal epithelium could participate in CDK development as a source of cytokines and gelatinases. Additionally, in HCE cells, UV-B- modulated cytokine and subsequent MMP secretion. Local inhibition of cytokine secretion and gelatinases may prevent CDK progression.