Pathogenesis of Keratoconus: The intriguing therapeutic potential of Prolactin-inducible protein

Sharif, Rabab; Bak‐Nielsen, Sashia; Hjortdal, Jesper; Karamichos, Dimitrios

doi:10.1016/j.preteyeres.2018.05.002

Cited by 89 publications

(79 citation statements)

References 201 publications

(235 reference statements)

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“…Yin et al reported a reduction of progesterone receptor (PR) and higher expression of androgen receptor (AR), where Ayan et al reported higher estrogen receptor (ER) and AR expressions in KC corneas. Our group reported higher mRNA levels of ER and lower AR, in KC-derived corneal stromal cells compared to healthy controls [41]. It is highly possible that these receptors are critical in maintaining the KC corneal homeostasis and are regulated by the abnormal hormone levels found in KC tears (DHEA-S, estrone, and estriol), as previously reported [12].…”

Section: Discussionsupporting

confidence: 72%

Gonadotropins in Keratoconus: The Unexpected Suspects

Karamichos

Barrientez

Nicholas

et al. 2019

Cells

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Keratoconus (KC) is the most common ectatic corneal disease with a significant visual acuity burden. The actual burden is intangible given that KC can disrupt daily activities (reading, driving, and various career paths). Despite decades of research and clinical studies, the etiology, onset, and pathobiology of KC remain a mystery. The purpose of this study was to investigate the role of gonadotropins in KC. We recruited 86 KC patients (63 males, 23 female), and 45 healthy controls (22 male, 23 female). Plasma samples were collected and analyzed using an enzyme-linked immunosorbent assay. Corneal stromal cells from KC and healthy controls, and human epithelial corneal cells, were also investigated for gonadotropin-related markers. Our results show significant alterations of LH/FSH in KCs, compared to healthy controls. Our data also reveals, for the first time, the existence of gonadotropins and their receptors in KC. Our study is the first to demonstrate the role of LH/FSH in KCs, and expand the list of organs known to express gonadotropins, or their receptors, to include the human cornea. Our findings suggest that the human cornea is capable of responding to gonadotropins, and propose an intriguing mechanism for the onset and/or progression of KC.

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Section: Discussionsupporting

confidence: 72%

Gonadotropins in Keratoconus: The Unexpected Suspects

Karamichos

Barrientez

Nicholas

et al. 2019

Cells

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“…Because sex hormones can act through receptors expressed in the ocular tissue, for example, the effects of androgens rely on the androgen receptors present in corneal tissue, they may be associated with various ocular pathologies. Although Clinical information about sex hormones in KCN patients is scarce, recent studies have investigated the role of hormonal changes on corneal structure in KCN patients [19,20]. Mckay (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that in ammation due to increased proin ammatory cytokines and other in ammatory factors has also been implicated in the pathogenesis of CKD [12,18]. Finally, recent studies have highlighted the effects of sex hormones on the corneas of KCN patients [19,20]. It has been postulated that the progression of CKD is linked to an increase in renal brosis resulting from the activation of the mineralocorticoid receptor (MR) related to aldosterone [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Rabab et al reported in their preliminary studies that exogenous DHEA led to signi cant upregulation of collagen type III and cellular bronectin suggesting that DHEA may drive human keratotic cornea towards a brotic change[20]. A similar brotic change related to androgen or miniralocorticoid may be the link between KCN and subsequent CKD development in male patients.…”

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confidence: 99%

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Association Between Chronic Kidney Disease and the Most Common Corneal Ectasia Disease (Keratoconus): A Nationwide Cohort Study

Jan

Weng

Wang

et al. 2020

Preprint

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Abstract Background The retrospective, nationwide, matched cohort study investigated the association between chronic kidney disease (CKD) and keratoconus (KCN), the most common corneal ectasia disease. Methods The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age-, sex-, and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the cumulative CKD incidence rate. Results The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95% confidence interval [CI] = 0.99–1.86, p = 0.0566). In total, 29 male KCN patients and 90 controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95% [CI] = 1.26–2.91; p = 0.0023) higher in male KCN patients than in controls. After adjusting for potential confounders, including hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients and male patients ≥ 40 years were 1.75 times (adjusted HR = 1.75, 95% [CI] = 1.14–2.68, p < 0.05), and 19.83 times (adjusted HR = 19.83, 95% CI = 8.75–44.97, p < 0.05) more likely to develop CKD, respectively. Conclusions We found that male KCN patients, particular male patients ≥ 40 years of age have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.

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“…Keratoconus (KC) is a common corneal condition characterized by progressive corneal thinning that results in corneal protrusion, 1 reduced vision and potential blindness. Prevalence of KC ranges from 0.17 in 1000 in the United States 2 to 47.89 in 1000 in Saudi Arabia.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Performance of Various Machine Learning Algorithms to Detect Subclinical Keratoconus

Cao

Verspoor

Sahebjada

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose: Keratoconus (KC) represents one of the leading causes of corneal transplantation worldwide. Detecting subclinical KC would lead to better management to avoid the need for corneal grafts, but the condition is clinically challenging to diagnose. We wished to compare eight commonly used machine learning algorithms using a range of parameter combinations by applying them to our KC dataset and build models to better differentiate subclinical KC from non-KC eyes. Methods: Oculus Pentacam was used to obtain corneal parameters on 49 subclinical KC and 39 control eyes, along with clinical and demographic parameters. Eight machine learning methods were applied to build models to differentiate subclinical KC from control eyes. Dominant algorithms were trained with all combinations of the considered parameters to select important parameter combinations. The performance of each model was evaluated and compared. Results: Using a total of eleven parameters, random forest, support vector machine and k-nearest neighbors had better performance in detecting subclinical KC. The highest area under the curve of 0.97 for detecting subclinical KC was achieved using five parameters by the random forest method. The highest sensitivity (0.94) and specificity (0.90) were obtained by the support vector machine and the k-nearest neighbor model, respectively. Conclusions: This study showed machine learning algorithms can be applied to identify subclinical KC using a minimal parameter set that are routinely collected during clinical eye examination. Translational Relevance: Machine learning algorithms can be built using routinely collected clinical parameters that will assist in the objective detection of subclinical KC.

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Pathogenesis of Keratoconus: The intriguing therapeutic potential of Prolactin-inducible protein

Cited by 89 publications

References 201 publications

Gonadotropins in Keratoconus: The Unexpected Suspects

Gonadotropins in Keratoconus: The Unexpected Suspects

Association Between Chronic Kidney Disease and the Most Common Corneal Ectasia Disease (Keratoconus): A Nationwide Cohort Study

Evaluating the Performance of Various Machine Learning Algorithms to Detect Subclinical Keratoconus

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