Corneal Innervation and Cellular Changes after Corneal Transplantation: An In Vivo Confocal Microscopy Study

Niederer, Rachael L; Perumal, Divya; Sherwin, Trevor; McGhee, Charles N J

doi:10.1167/iovs.06-0538

Cited by 117 publications

(81 citation statements)

References 42 publications

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“…31 IVCM assessment of the subbasal nerve plexus revealed a marked increase in nerve density in the central cornea of three patients compared to the control group and to other healthy human corneas assessed by the same laser-scanning IVCM technique. 32,33 This finding is notably contradictory to one report of decreased subbasal nerve density in heterozygous Pax6 mice. 31 We present, however, the first subbasal nerve density values in human cases, and the highest subbasal nerve density observed in vivo to date.…”

Section: Discussioncontrasting

confidence: 74%

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

et al. 2012

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Objective: To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families. less thanbrgreater than less thanbrgreater thanDesign: Prospective, observational, comparative case series. less thanbrgreater than less thanbrgreater thanParticipants: A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia. less thanbrgreater than less thanbrgreater thanMethods: Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM). less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt. less thanbrgreater than less thanbrgreater thanResults: In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P andlt; 0.001 for both), and corneal thickness was increased (P = 0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls. less thanbrgreater than less thanbrgreater thanConclusions: Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy. less thanbrgreater than less thanbrgreater thanFinancial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Funding Agencies|European Union||Crown Princess Margaretas Foundation for the Visually Impaired||Swedish Eye Fund||Carmen and Bertil Regners Foundation||David and Beth Dahlins Foundation||King Gustav V and Queen Victorias Freemasons Foundation||County Council of Ostergotland||Association of the Blind in Ostergotland||

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Section: Discussioncontrasting

confidence: 74%

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

et al. 2012

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“…An experienced examiner (ZG) analyzed the subbasal nerve plexus as described before. 19 Briefly, nerve density was assessed by measuring the total length of the nerve fibers in micrometers per frame (0.06 mm 2 ). The number of total nerves was also measured and it was defined as the number of all nerves, including main nerve trunks and branches in one image.…”

Section: Image Analysismentioning

confidence: 99%

“…[10][11][12] Moreover, the architecture of the corneal subbasal nerve plexus has been investigated, with the aid of confocal microscopy, in patients with keratoconus, Sjogren syndrome, or dry eye, as well as after penetrating keratoplasty, laser in situ keratomileusis, or photorefractive keratectomy. [13][14][15][16][17][18][19][20][21] Within this context, the purpose of this study was to investigate the corneal sensitivity in patients with PCG and correlate the clinical findings with the corneal subbasal nerve density by use of LSCM.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16][17][18] Furthermore, a positive association between corneal nerve regeneration and corneal sensitivity has been observed after penetrating keratoplasty and laser refractive surgery. [19][20][21] Rosenberg et al 27 have reported that reduction of subbasal plexus nerve fibers correlates with loss of corneal sensitivity in patients with diabetic neuropathy, while tortuosity of subbasal nerves correlated significantly with the severity of diabetic neuropathy. Hamrah et al 28 have recently described significant morphological changes in corneal subbasal nerve plexus in patients with herpes simplex keratitis and showed that reduction of nerve density correlated significantly with loss of corneal sensitivity in such patients.…”

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confidence: 99%

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Corneal sensitivity and morphology of the corneal subbasal nerve plexus in primary congenital glaucoma

Gatzioufas

Labiris

Hafezi

et al. 2014

Eye

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Background To quantify the corneal subbasal nerve density and the total number of nerve fibers in primary congenital glaucoma (PCG) and to evaluate their impact on corneal sensitivity. Methods Forty eyes of 26 PCG patients were compared with 40 eyes randomly selected from 40 non-glaucoma patients who populated the control group. Central corneal sensitivity (CCS) was assessed by means of Cochet-Bonnet esthesiometry. The mean subbasal nerve density and the total number of nerve fibers were quantified by laserscanning confocal microscopy. Normality of data was assessed by Kolmogorov-Smirnov testing. Differences in parameters were assessed with Student's t-test, while correlations with CSS were assessed with Pearson's correlation. Results Significant differences were identified in the mean subbasal nerve density (2108 ± 692 mm in PCG, 2642 ± 484 mm in controls, P ¼ 0.003) and in the total number of nerve fibers (12.3±4.2 in PCG, 15.4±3.1 in controls, P ¼ 0.02). Both groups presented comparable mean CCS and tortuosity. Both groups presented strong correlations between CCS and mean nerve density (r ¼ 0.57 in PCG, r ¼ 0.67 in controls, all Po0.05), and between CCS and total number of nerve fibers (r ¼ 0.55 in PCG, r ¼ 0.56 in controls, all Po0.05). Conclusion PCG exerts significant changes in both the mean subbasal nerve density and the total number of nerve fibers. However, these changes do not appear to affect central corneal sensitivity.

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“…Corneal Confocal Microscopy (CCM) is a rapid non-invasive in vivo clinical technique for capturing images of the different corneal layers [2]. Morphological alterations in the epithelium, stroma and endothelium provide insights into a variety of corneal diseases [3,4] and assessment of the effects of wearing contact lenses [1], LASIK or PRK [5], fungal keratitis [6], corneal transplantation [7] or conditions such as keratoconus [8,9]. CCM has also been used in the assessment of peripheral neuropathies [10,11,12,13,14,15,16,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

A fully automatic nerve segmentation and morphometric parameter quantification system for early diagnosis of diabetic neuropathy in corneal images

Al-Fahdawi

Qahwaji

Al-Waisy

et al. 2016

Computer Methods and Programs in Biomedicine

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Corneal Innervation and Cellular Changes after Corneal Transplantation: An In Vivo Confocal Microscopy Study

Abstract: Laser scanning in vivo confocal microscopy highlights profound reductions in cell density at every level of the transplanted cornea and alterations to the subbasal plexus that are still apparent up to 40 years after penetrating keratoplasty.

Cited by 117 publications

References 42 publications

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

Corneal sensitivity and morphology of the corneal subbasal nerve plexus in primary congenital glaucoma

A fully automatic nerve segmentation and morphometric parameter quantification system for early diagnosis of diabetic neuropathy in corneal images

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