An in depth analysis of histopathological characteristics found in keratoconus

Sykakis, Evripidis; Carley, Fiona; Irion, Luciane; Denton, J.; Hillarby, M. C.

doi:10.1097/pat.0b013e3283511b42

Cited by 72 publications

(63 citation statements)

References 29 publications

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“…161 However, in contrast with that investigation, two studies did not find positive results for antibody markers for CD68 in keratoconus. 162, 163 Sykakis et al 164 reported in 2012 that they identified both isolated and aggregated nuclei at sites of Bowman's breaks in keratoconic corneas, for which the origin could not be identified (they did not look for the immunohistochemical expression of anti-CD68 antibody).…”

Section: Resultsmentioning

confidence: 99%

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

293

199

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Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

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Section: Resultsmentioning

confidence: 99%

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

293

199

View full text Add to dashboard Cite

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“…2 Light and electron microscopy studies have shown that in keratoconus (KC), BL undergoes disintegration that leads to irregular thinning, fragmentation and then breaks within the layer. 3–8 Those structural changes are noted when the stroma is only minimally affected suggesting that BL changes are possibly early pathological changes in the disease process. 4, 9 Ocular pathologists have long used those signs for the in-vitro diagnosis of KC in the pathology laboratory under light microscopy.…”

Section: Introductionmentioning

confidence: 99%

“…4, 9 Ocular pathologists have long used those signs for the in-vitro diagnosis of KC in the pathology laboratory under light microscopy. 3 Nevertheless, those signs are not useful for clinicians owing to the simple fact that clinicians do not have the capability to visualize this layer in vivo.…”

Section: Introductionmentioning

confidence: 99%

The Use of Bowman's Layer Vertical Topographic Thickness Map in the Diagnosis of Keratoconus

et al. 2014

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Purpose To evaluate the use of Bowman’s layer (BL) vertical topographic thickness maps in diagnosing keratoconus (KC). Design Prospective, case control, interventional case series. Participants 42 eyes; 22 eyes of 15 normal subjects and 20 eyes of 15 KC patients. Intervention BL 2-dimensional 9 mm vertical topographic thickness maps were created using custom-made ultra high-resolution optical coherence tomography. Main Outcome Measures BL average and minimum thicknesses of the inferior half of the cornea, Bowman’s ectasia index (BEI; defined as BL minimum thickness of the inferior half of the cornea divided by BL average thickness of the superior half of the cornea multiplied by 100), BEI-Max (defined as BL minimum thickness of the inferior half of the cornea divided by BL maximum thickness of the superior half of the cornea multiplied by 100), KC patients’ Keratometric astigmatism (Ast-K) and average keratometric readings (Avg-K). Results In KC patients, BL vertical thickness maps disclosed localized relative inferior thinning of the BL. Inferior BL average thickness (normal=15±2, KC=12±3 μm), inferior BL minimum thickness (normal=13±2, KC=7±3 μm), BEI (normal=91±7, KC=48±14) and BEI-Max (normal=75±8; KC=40±13) all showed highly significant differences in KC compared to normal subjects (P<0.001). Receiver-operating characteristics (ROC) curve analysis showed excellent predictive accuracy for BEI and BEI-max with 100% sensitivity and specificity (area under the curve or AUC of 1) with cut-off values of 80 and 60, respectively. AUC of inferior BL average thickness and minimum thickness were 0.87 and 0.96 with sensitivity of 80% and 93%, respectively and specificity of 93% and 93%, respectively. Inferior BL average thickness, inferior BL minimum thickness, BEI and BEI-Max correlated highly to Ast-K (R=−0.72; −0.82; −0.84 and −0.82, respectively; P<0.001) and to Avg-K (R=−0.62; P<0.001, R=−0.59; P=0.001, R=−0.60; P<0.001 and R=−0.59, P=0.001, respectively). Conclusions BL vertical topographic thickness maps of KC patients disclose characteristic localized relative inferior thinning. Inferior BL average thickness, inferior BL minimum thickness, BEI and BEI-max are qualitative and quantitative indices for the diagnosis of KC that accurately correlate with the severity of KC. In our pilot study, BEI and BEI-max showed excellent accuracy, sensitivity and specificity in the diagnosis of KC.

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“…8 Histopathologic analysis of corneal ectasia have shown thinning of the epithelium, usually overlying the steepest portion of the cornea, breaks in Descemet’s membrane, fragmentation of Bowman layer, and scarring. 8,9 The corneal epithelium has a rapid cell turnover and is highly reactive to asymmetries in the shape of the underlying stromal surface. Epithelial layer remodeling may therefore have a significant impact in corneal topographic measurements, corneal warpage patterns, and early detection of corneal ectatic processes.…”

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confidence: 99%

SD-OCT Analysis of Regional Epithelial Thickness Profiles in Keratoconus, Postoperative Corneal Ectasia, and Normal Eyes

Km¹,

Ce²,

Rd³

et al. 2013

J Refract Surg

155

117

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PURPOSE-To assess corneal microarchitecture and regional epithelial thickness profile in eyes with keratoconus, postoperative corneal ectasia, and normal unoperated eyes using spectraldomain optical coherence tomography (SD OCT). METHODS-Regional corneal epithelial thickness profiles of eyes with keratoconus (KC) and postoperative corneal ectasia (Ectasia)were measured with anterior segment SC OCT (Optovue RTVue-100, Optovue Inc., Fremont, CA) and compared retrospectively to those of normal eyes (Control). Epithelial thickness was assessed at 21 points, 0.5 mm apart, across the central 6-mm of the corneal apex in the horizontal and vertical meridians.RESULTS-One hundred twenty eyes were evaluated, including 49 eyes from 29 patients with KC, 32 eyes from 16 patients with Ectasia, and 39 eyes from 21 control patients. Average epithelial thickness at the corneal apex was 41.18±6.47μm (range 30 to 51 μm) in eyes with KC, 46.5±6.72μm in eyes with ectasia (range 34 to 60 μm), and 50.45±3.92 μm in normal eyes (range 42 to 55 μm). Apical epithelial thickness was significantly thinner in eyes with KC (p <.0001) and ectasia (p=.0007) than it was in controls. Epithelial thickness ranges in all other areas varied widely for KC (SD, range 21 to 101 μm) and ectasia (SD, range 30 to 82 μm) compared to controls (SD, range 43 to 64), p = .0063 CONCLUSION-Central epithelial thickness was, on average, significantly thinner in ectatic corneas compared to controls; however, both central and regional epithelial thickness was highly irregular and variable in corneas with keratoconus and postoperative corneal ectasia. These thickness variations may alter preoperative topographic features and measurements in unpredictable ways, especially steepest K values. Regional epithelial thickness cannot be assumed to be uniform in ectatic corneas and therefore may require direct measurement when considering New treatment modalities are demonstrating significant potential efficacy for ectatic corneal disorders such as keratoconus and postoperative corneal ectasia, including corneal collagen cross linking (CXL), intracorneal ring segments (ICRS), and limited topography-guided laser ablation, with variable success rates. 1-7 While these ectatic diseases comprise a heterogeneous population, the end stage histopathological changes are quite similar. 8 Histopathologic analysis of corneal ectasia have shown thinning of the epithelium, usually overlying the steepest portion of the cornea, breaks in Descemet's membrane, fragmentation of Bowman layer, and scarring. 8,9 The corneal epithelium has a rapid cell turnover and is highly reactive to asymmetries in the shape of the underlying stromal surface. Epithelial layer remodeling may therefore have a significant impact in corneal topographic measurements, corneal warpage patterns, and early detection of corneal ectatic processes. 10,11 CXL and ICRS both require a minimum corneal depth to prevent corneal endothelial damage for CXL or segment extrusion for ICRS. In both procedures, corneal thickness i...

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An in depth analysis of histopathological characteristics found in keratoconus

Cited by 72 publications

References 29 publications

Keratoconus: an inflammatory disorder?

Keratoconus: an inflammatory disorder?

The Use of Bowman's Layer Vertical Topographic Thickness Map in the Diagnosis of Keratoconus

SD-OCT Analysis of Regional Epithelial Thickness Profiles in Keratoconus, Postoperative Corneal Ectasia, and Normal Eyes

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