Recurrence or Re-emergence of Keratoconus – What is the Evidence Telling Us? Literature Review and Two Case Reports

Bergmanson, Jan P.G.; Goosey, John D.; Patel, Chirag; Mathew, Jessica H.

doi:10.1016/j.jtos.2014.05.004

Cited by 34 publications

(20 citation statements)

References 26 publications

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“…Bergmanson et al 12 suggested that this might be due to the presence of subclinical KC in the graft, which progressed and manifested after the surgery rather than an actual reoccurrence of KC. Nevertheless, this does not fully eliminate the possibility of peripheral involvement and migration from the host tissue to the donor’s graft.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural study of peripheral and central stroma of keratoconus cornea

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Ultrastructural study of peripheral and central stroma of keratoconus cornea

et al. 2017

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“…The only available treatment for progressive keratoconus, corneal collagen crosslinking, is an effective method of slowing down or halting progression in keratoconus 5. However, this modality does not address the underlying biological processes that lead to disease pathogenesis, nor do other treatments aimed at visual rehabilitation, such as contact lens wear, intracorneal ring segments, or corneal tranplants 6. Currently, there is no small molecule intervention strategy for the treatment of keratoconus either to halt or reverse the progression of this disease.…”

mentioning

confidence: 99%

Small Molecule Modulation of the Integrated Stress Response Governs the Keratoconic Phenotype In Vitro

Soiberman

Shehata

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The degenerative corneal disease keratoconus is a leading indicator for corneal transplant with an unknown etiology. We recently identified the activation of the integrated stress response (ISR) in ex vivo human corneas and in vitro cell culture. Utilizing small molecules to modulate the ISR we sought to investigate the effects of stimulating the ISR in healthy cells to recapitulate aspects of the in vitro keratoconic phenotype and whether relieving the ISR signaling would recover the disease phenotype. METHODS. Corneal fibroblasts were extracted from patients undergoing corneal transplant or unaffected cadaverous donor limbal rings. Cells were exposed to the DNA damage-inducible protein (GADD34) inhibitor SAL003 to stimulate the ISR, or Trans-ISRIB to relieve ISR signaling pathway. Collagen production was assessed through hydroxyproline production, Sirius Red incorporation, or quantitative (q)PCR. Western blotting, hydroxyproline, and qPCR were used to assess components of the ISR pathway and collagen production. RESULTS. ISR stimulation through SAL003 resulted in significant decrease of hydroxyproline and COL1A1 transcription and eventual apoptosis in normal fibroblasts. Patient (KC) fibroblast production of hydroxyproline was increased in response to ISRIB, while matrix metalloproteinase (MMP)9 production was lowered. The prospective biomarker of keratoconus prolactin-inducible factor was also upregulated in KC fibroblast cultures in response to ISRIB. Inflammatory markers TNFa and IL-1b were unaffected. CONCLUSIONS. Activation of the ISR is sufficient to recapitulate many key aspects of the KC phenotype in unaffected cells in vitro. Inhibition of the ISR also relieves many of the hallmarks of KC in affected cells. Therefore, targeting of the ISR through small molecules is a potential therapeutic path for small molecule treatment of keratoconus.

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“…Slit-scanning provides pachymetry values, but repeatability and posterior curvature mapping are inaccurate. Scheimpflug imaging is the preferred modality by most corneal surgeons because it provides precise corneal thickness and posterior elevation with good repeatability [ 18 ].…”

Section: Clinical Features and Visual Disturbancesmentioning

confidence: 99%

“…After PK for KC, postoperative corneal ectasia has been estimated to occur in 6% to 11% of the patients at 20 to 25 years after surgery [ 3 ]. The latency period is, on average, 19 years after PK, paralleling the natural evolution of keratoconus in adolescence [ 7 , 18 ]. According to these data, ectasia following PK is a rare condition that has been described as developing as early as seven years and usually more than ten years following suture removal and increasing up to 20–25-years after surgery.…”

Section: Frequency Of Corneal Ectasia After Keratoplastymentioning

confidence: 99%

Post Penetrating Keratoplasty Ectasia: Incidence, Risk Factors, Clinical Features, and Treatment Options

Moramarco

Gardini

Iannetta

et al. 2022

JCM

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BACKGROUND: Corneal transplantation in keratoconus (KC) patients is generally considered to be successful with a high grade of patient satisfaction. Long-term studies suggest a 6% to 11% probability of KC recurrence manifested by keratometric instability and progressive corneal ectasia. METHODS: We propose to review the frequency, risk factors for the development, and the surgical options for the correction of high irregular astigmatism due to late graft ectasia following penetrating keratoplasty (PK). RESULTS: Post-keratoplasty ectasia is characterized by increasing corneal steepening with myopic shift and high irregular astigmatism, developing years or decades after PK, mostly occurring in KC patients. Contact lenses may adequately improve the visual acuity; however, because these patients are often elderly and intolerant to hard contact lenses, ultimately a surgical correction is proposed to the patient. Compressive suture and corneal wedge resection may improve corneal astigmatism, but the outcomes are unpredictable and often temporary. For this reason, a larger PK graft is often proposed for surgical rehabilitation with the consequence of removing more of the recipient’s healthy endothelium and exposing the patient to a renewed immunogenic stimulus and short-term graft failure for endothelial decompensation. More recently, lamellar keratoplasty using various techniques has been proposed as an alternative to PK in order to maximize the visual outcomes and minimize the complications. CONCLUSIONS: Management of advanced corneal ectasia is a significant challenge for corneal surgeons. Many surgical approaches have been developed, so there is a large arsenal of surgical operations to correct post-PK ectasia. Among them, large-diameter anterior lamellar keratoplasty may be a viable, safer, and effective alternative to PK for the correction of post-keratoplasty ectasia.

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Recurrence or Re-emergence of Keratoconus – What is the Evidence Telling Us? Literature Review and Two Case Reports

Cited by 34 publications

References 26 publications

Ultrastructural study of peripheral and central stroma of keratoconus cornea

Ultrastructural study of peripheral and central stroma of keratoconus cornea

Small Molecule Modulation of the Integrated Stress Response Governs the Keratoconic Phenotype In Vitro

Post Penetrating Keratoplasty Ectasia: Incidence, Risk Factors, Clinical Features, and Treatment Options

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