Corneal nerves in refractive surgery and dry eye

This study aimed to investigate the morphology and function of corneal sensory nerves in 1) patients after corneal refractive surgery and 2) patients with dry eye due to Sjögren's syndrome. A third aim was to explore the possible correlation between cytokines detected in tears and development of post-PRK subepithelial haze. The main methods used were tear fluid ELISA analysis, corneal in vivo confocal microscopy, and noncontact esthesiometry. The results revealed that after PRK a positive correlation exists between the regeneration of subbasal nerves and the thickness of regenerated epithelium. Pre- or postoperative levels of the tear fluid cytokines TGF-β1, TNF-α, or PDGF-BB did not correlate with the development of corneal haze objectively estimated by in vivo confocal microscopy 3 months after PRK. After high myopic LASIK, a discrepancy between subjective dry eye symptoms and objective signs of dry eye was observed. The majority of patients reported ongoing dry eye symptoms even 5 years after LASIK, although no objective clinical signs of dry eye were apparent. In addition, no difference in corneal sensitivity was observed between these patients and controls. Primary Sjögren's syndrome patients presented with corneal hypersensitivity, although their corneal subbasal nerve density was normal. However, alterations in corneal nerve morphology (nerve sprouting and thickened stromal nerves) and an increased number of antigen-presenting cells among subbasal nerves were observed, implicating the presence of an ongoing inflammation. Based on these results, the relationship between nerve regeneration and epithelial thickness 3 months after PRK appears to reflect the trophic effect of corneal nerves on epithelium. In addition, measurement of tear fluid cytokines may not be suitable for screening patients for risk of scar (haze) formation after PRK. Presumably, at least part of the symptoms of "LASIK-associated dry eye" are derived from aberrantly regenerated and abnormally functioning corneal nerves. Thus, they may represent a form of corneal neuropathy or "phantom pain" rather than conventional dry eye. Corneal nerve alterations and inflammatory findings in Sjögren's syndrome offer an explanation for the corneal hypersensitivity or even chronic pain or hyperalgesia often observed in these patients. In severe cases of disabling chronic pain in patients with dry eye or after LASIK, when conventional therapeutic possibilities fail to offer relief, consultation of a physician specialized in pain treatment is recommended.Väitöskirjatutkimukseni tavoitteena oli selvittää sarveiskalvohermojen toimintaa ja morfologiaa taittovirhekirurgian (PRK ja LASIK) jälkeen sekä Sjögrenin syndroomaan liittyvässä kuivasilmäisyydessä. Sarveiskalvon taittovirhekirurgian tiedetään vaurioittavan sarveiskalvon tuntohermoja, jotka ovat merkittäviä mm. kyynelnestetuotannon säätelyssä. Tavoitteena oli myös selvittää kyynelnesteen kasvutekijäpitoisuuksien yhteyttä taittovirhekirurgian (PRK) jälkeiseen haavan paranemiseen. Tutkimuksessa käytetyt pääasialliset menetelmät olivat kyynelnesteen kasvutekijäpitoisuus-määritys, sarveiskalvon in vivo konfokaalimikroskopia ja sarveiskalvon tuntomittaus. Kolme kuukautta taittovirhekirurgian (PRK) jälkeen sarveiskalvon pintakerroksen eli epiteelin paksuus korreloi epiteelinalaisten hermojen regeneraation, osaltaan todistaen jo aiemmin tiedettyä sarveiskalvohermojen merkitystä epiteelin kasvun säätelyyn. Kyynelnesteen kasvutekijäpitoisuuksilla ennen toimenpidettä tai sen jälkeen ei näyttänyt olevan yhteyttä taittovirheleikkauksen (PRK) jälkeiseen arpikudoksen määrään kolmen kuukauden kuluttua toimenpiteestä. Näin ollen kyynelnesteen potentiaalisesti arpea aiheuttavien kasvutekijöiden analysointi ei näyttäisi olevan käyttökelpoisin tapa löytää potilaita, joilla olisi suurentunut riski saada arpisamentumaa taittovirhekirurgian (PRK) jälkeen. Jopa viisi vuotta LASIK -leikkauksen jälkeen suurin osa (55 %) potilaista raportoi silmän kuivuusoireista, vaikka tavanomaiset kuivasilmäisyystestien tulokset olivat normaalit. Yllättäen, myöskään sarveiskalvon tuntomittaustuloksissa ei ollut eroa 2 5 vuotta LASIK (yli -10D) leikkauksen jälkeen ikä- ja sukupuolivakioituihin kontrolleihin verrattuna. Todennäköisesti osa potilaiden ilmoittamista kuivasilmäisyysoireista ei johdukaan silmänpinnan kuivuudesta, vaan epänormaalisti regeneroituneista ja toimivista tuntohermoista. Vaikeimmissa tapauksissa voitaisiinkin puhua enemmänkin sarveiskalvon neuropaattisesta kroonisesta kivusta, tai jopa haamukivusta. Sjögrenin syndroomaa sairastavilla kuivasilmäisyyspotilailla todettiin sarveiskalvon hypersensitiviteetti, eli hyvin pienetkin tuntoärsykkeet olivat aistittavissa. Sarveiskalvon hermotiheys oli kuitenkin normaali ikä- ja sukupuolivakioituihin kontrolleihin verrattuna, mutta hermojen morfologia erilainen. Stroomahermot olivat paksumpia, ja epiteelinalaisissa hermoissa tavattiin versomista "sprouting" hermojen degeneraation/regeneraation merkkinä. Lisäksi epiteelinalaisten hermojen tasossa tavattiin tulehdussoluja, merkkinä tulehdusreaktiosta eli inflammaatiosta. Nämä sarveiskalvohermoihin liittyvät poikkeavat löydökset tarjoavat selityksen sarveiskalvon hypersensitiivisyydelle, tai jopa hyperalgesialle, joita usein tavataan Sjögrenin syndrooma potilailla. Sjögrenin syndroomaan tai taittovirhekirurgiaan liittyvä "kuivasilmäisyys"-oireisto saattaa aiheuttaa hyvinkin hankalia silmien kiputiloja. Mikäli tavanomaiset hoitokeinot eivät tuo apua, on kivunhoitoon erikoistuneen lääkärin konsultaatio suositeltavaa

Kaihi

KÄYPÄ HOITO -SUOSITUS (Päivitystiivistelmä

Dystrophia Helsinglandica - corneal morphology, topography and sensitivity in a hereditary corneal disease with recurrent erosive episodes

Purpose: The aim of this study was to describe the morphology, corneal topography and sensitivity in individuals with Dystrophia Helsinglandica. This autosomal dominant corneal disease is characterized by recurrent corneal erosive episodes and progressive subepithelial fibrosis not significantly affecting visual acuity. Methods: The corneas of nine affected and nine unaffected individuals were examined using slit-lamp biomicroscopy, in vivo confocal microscopy (IVCM) and videokeratography. Corneal mechanical sensitivity was also measured using a non-contact esthesiometer. Results: Slit-lamp biomicroscopy revealed that the affected individuals represented different stages of corneal changes, from a nearly normal cornea to subepithelial fibrosis of the central cornea. Corneal changes in affected individuals did not significantly decrease the best spectacle-corrected visual acuity. In vivo confocal microscopy detected morphological changes in the epithelium and stroma. Subepithelial opacity formation including altered keratocytes could be found in the anterior stroma in all affected eyes. With the exception of two eyes (one affected and one unaffected), all videokeratographies showed irregular astigmatism. Corneal sensitivity was significantly lower in affected individuals (p = 0.01). Age and corneal sensitivity showed no correlation. Conclusion: The main morphological findings in affected individuals were discrete and progressive subepithelial fibrosis, in the in vivo confocal microscope corresponding to optically dense extracellular matrix and activated keratocytes. Subbasal nerve morphology was changed in the affected family members who also showed a decreased corneal sensitivity. The findings are per se not specific to the disease. The changes probably reflect a healing response to erosive events on the corneal surface influenced by the genotype

Epithelial recurrent erosion dystrophy (ERED) from the splice site altering COL17A1 variant c.3156C>T in families of Finnish-Swedish ancestry

Purpose: To describe four Finnish families with epithelial recurrent erosion dystrophy (ERED) caused by the pathogenic variant c.3156C>T in collagen type XVII alpha 1 chain gene (COL17A1).Methods: Eleven affected and two unaffected individuals underwent clinical ophthalmological examination, anterior segment photography, and corneal topography. Two of them underwent phototherapeutic keratectomy (PTK). Genetic analysis included both next-generation and Sanger sequencing. Specimens from the manual keratectomy of one patient were available for ophthalmic pathologic examination, including immunohistochemistry.Results: The common splice-site altering synonymous variant c.3156C > T, p.(Gly1052=) in COL17A1 was confirmed in 15 individuals with ERED from the four families. Subepithelial corneal scarring grades varied and increased with age, leading to decreased best- -corrected visual acuity. PTK improved vision in 58- and 67-year-old individuals without reactivating the disease. The keratectomy specimens showed an uneven epithelium and a spectrum of basement membrane abnormalities, including breaks, fragmentation, multiplication and entrapment within the subepithelial scar, reflecting recurrent erosions. The stromal cells consisted of varying proportions of bland and activated fibroblasts and myofibroblasts, reflecting different ages of scars. The family with the largest number of known affected generations originated from Southern Sweden.Conclusion: The phenotype in the Finnish ERED families is consistent with earlier reports of the c.3156C > T variant, although the severity has varied between reports. The phenotype may be modulated by other genes. This study suggests a likely founder effect of the variant in both Finnish and Swedish populations due to their shared population histories. If vision is compromised, PTK can be considered especially in older patients.Peer reviewe