Relapsirajući polihondritis i leukemična infiltracija u bolesnika s mijelodisplastičnim sindromom

A 56-year-old female patient with myelodysplastic syndrome is presented, in whom pathogenetically diverse mechanisms led to the development of severe sensorineural hearing loss and bilateral blindness. The patient had suffered from myelodysplastic syndrome from 2003. One year after verification of the diagnosis, she presented to the Department of Ophthalmology for ptosis and edema of the right eyelid, exophthalmia, visual impairment, and restricted ocular movement. The discomforts persisted for four weeks to result in the loss of vision. This was followed by impaired hearing in the right ear, accompanied by vertigo. Two months later, the same occurred in the left ear, preceded by visual impairment in the left eye with identical symptomatology as in the right eye. The disease eventually resulted in bilateral hearing loss and blindness. Laboratory findings were consistent with the clinical picture. Audiologic testing confirmed sensorineural deafness in the right ear first, followed by severe conductive hearing loss in the left ear. Computed tomography and nuclear magnetic resonance findings of the ear were normal. Computed tomography of the orbits showed bilateral optic nerve thickening. There was bilateral absence of visual evoked potentials and presence of relative afferent pupillary defect. Analysis of the patient’s findings and comparison with literature reports suggested the role of two mechanisms, i.e. relapsing polychondritis and leukemic cell infiltration, in the pathogenesis of myelodysplastic syndrome symptomatology.Prikaz slučaja 56-godišnje bolesnice sa sindromom mijelodisplazije, u koje patogenentski dvojni mehanizmi dovode do razvoja teške senzorineuralne gluhoće i sljepoće. Sindrom mijelodisplazije se verificira 2003. godine. Godinu dana kasnije razvijaju se oteklina vjeđa, egzoftalmija, poremećaj vida i reducirani pomaci očne jabučice desnog oka. Poteškoće završavaju sljepoćom desnog oka. Sljepoća je praćena naglim gubitkom sluha na desnom uhu, s hipotonijom perifernog vestibularnog osjetila. Dva mjeseca kasnije sljepoća i gluhoća zahvaćaju lijevo oko i lijevo uho. Osnovna bolest se komplicira obostranom sljepoćom i gluhoćom. Biokemijski nalazi prate kliničku sliku. Audiološka testiranja potvrđuju senzorinerulanu nagluhost, pa gluhoću na desnom uhu, kasnije i na lijevom. Kompjutorizirana tomografija i nalaz magnetske rezonancije pokazuju uredan nalaz piramida sljepoočnih kostiju i zadebljanje očnog živca obostrano. Usporedo postoji obostrano odsutan VEP odgovor i relativni aferentni pupilarni defekt. Analiza učinjenih pretraga i usporedba sa spoznajama iz literature upućuje na sudjelovanje dvaju mehanizama, tj. relapsirajućeg polihondritisa i leukemične celularne infiltracije, u sklopu patogeneze sindroma mijelodisplazije

Relapsirajući polihondritis i leukemična infiltracija u bolesnika s mijelodisplastičnim sindromom

A 56-year-old female patient with myelodysplastic syndrome is presented, in whom pathogenetically diverse mechanisms led to the development of severe sensorineural hearing loss and bilateral blindness. The patient had suffered from myelodysplastic syndrome from 2003. One year after verification of the diagnosis, she presented to the Department of Ophthalmology for ptosis and edema of the right eyelid, exophthalmia, visual impairment, and restricted ocular movement. The discomforts persisted for four weeks to result in the loss of vision. This was followed by impaired hearing in the right ear, accompanied by vertigo. Two months later, the same occurred in the left ear, preceded by visual impairment in the left eye with identical symptomatology as in the right eye. The disease eventually resulted in bilateral hearing loss and blindness. Laboratory findings were consistent with the clinical picture. Audiologic testing confirmed sensorineural deafness in the right ear first, followed by severe conductive hearing loss in the left ear. Computed tomography and nuclear magnetic resonance findings of the ear were normal. Computed tomography of the orbits showed bilateral optic nerve thickening. There was bilateral absence of visual evoked potentials and presence of relative afferent pupillary defect. Analysis of the patient’s findings and comparison with literature reports suggested the role of two mechanisms, i.e. relapsing polychondritis and leukemic cell infiltration, in the pathogenesis of myelodysplastic syndrome symptomatology.Prikaz slučaja 56-godišnje bolesnice sa sindromom mijelodisplazije, u koje patogenentski dvojni mehanizmi dovode do razvoja teške senzorineuralne gluhoće i sljepoće. Sindrom mijelodisplazije se verificira 2003. godine. Godinu dana kasnije razvijaju se oteklina vjeđa, egzoftalmija, poremećaj vida i reducirani pomaci očne jabučice desnog oka. Poteškoće završavaju sljepoćom desnog oka. Sljepoća je praćena naglim gubitkom sluha na desnom uhu, s hipotonijom perifernog vestibularnog osjetila. Dva mjeseca kasnije sljepoća i gluhoća zahvaćaju lijevo oko i lijevo uho. Osnovna bolest se komplicira obostranom sljepoćom i gluhoćom. Biokemijski nalazi prate kliničku sliku. Audiološka testiranja potvrđuju senzorinerulanu nagluhost, pa gluhoću na desnom uhu, kasnije i na lijevom. Kompjutorizirana tomografija i nalaz magnetske rezonancije pokazuju uredan nalaz piramida sljepoočnih kostiju i zadebljanje očnog živca obostrano. Usporedo postoji obostrano odsutan VEP odgovor i relativni aferentni pupilarni defekt. Analiza učinjenih pretraga i usporedba sa spoznajama iz literature upućuje na sudjelovanje dvaju mehanizama, tj. relapsirajućeg polihondritisa i leukemične celularne infiltracije, u sklopu patogeneze sindroma mijelodisplazije

Ultraviolet Light and Pterygium

The purpose of this study was to evaluate the contribution of ultraviolet light (UV) as a causal factor of primary and pterygium recurrence. A conjuctival autograft transplantation was a surgical method of pterygium treatment. In the first group (38 eyes) were patients with primary and recurrent pterygium exposed to sun (worked outdoors), evaluating geodemographic status, and in the second group (20 eyes) were patients who were not. During 6–12 months of follow up recurrence rate after surgical removal was 27% in the first group and 10% in the second one. UV light seems to have an important role in cause of primary and recurrent pterygium

Association Between Diverse Diabetic Treatments and Duration of Diabetes Mellitus According to Progression of Diabetic Retinopathy: Experience From a Small Regional Hospital

Introduction: Research objectives of present study were to examine sex and age-related specifics of diabetic retinopathy according to the therapy approach and duration of diabetes mellitus. The study also aimed to determine the association between the presence of diabetic retinopathy and diabetes duration as a prognostic factor of retinopathy progression in such patients. Materials and Methods: The study was designed as a retrospective study and included 289 patients with diabetic retinopathy, who were treated at the Department of Ophthalmology of the General Hospital “Dr. Josip Benčević” in Slavonski Brod during the period from 2019 to 2020. Results: 176 patients were treated with oral antidiabetic drugs (OAD), while 113 patients were insulin-dependent. The median age of patients treated with OAD was 77 years. Diabetic retinopathy was present in 35 (19.9%) patients, of whom 33 (18.8%) had non-proliferative diabetic retinopathy, while 2 patients (1.1%) had proliferative diabetic retinopathy. The median age of the insulin-dependent patients was 79 years. Diabetic retinopathy was present in 54 patients (47.8%), non-proliferative diabetic retinopathy was diagnosed in 51 patients (45.1%), while proliferative diabetic retinopathy was diagnosed in only 3 (2.7%) patients. There was a significant difference between the presence of diabetic retinopathy and diabetes duration (P<0.001), as well as between the therapy approach and diabetes duration (⍺<0.001). Conclusion: Various hypotheses have been proposed to explain the worsening of diabetic retinopathy, and we assume that the therapy approach, duration of diabetes and HbA1c have a significant role in retinopathy progression. Hereby, we emphasize that, although there have been significant advances, there is still a pressing need for a better understanding of a new therapeutic modality, new tools for identifying high-risk patients and continued monitoring in order to intervene effectively before vision loss occurs. Further research is needed to identify and implement the best practices to increase diabetic eye screening rates in the long term

Povezanost serumske koncentracije vitamina d i glaukoma kod žena

The aim of the study was to determine whether serum vitamin D level is lower in female patients with glaucoma as compared with control group. The mechanism by which vitamin D reduces intraocular pressure is not fully clarified. Almost all tissues possess vitamin D receptor (VDR). The mice lacking VDR (VDR knockout mice) have greatly contributed to the understanding of the general vitamin D physiologic function. VDR has been found in some ganglion layer cells, external and internal nuclear layers of retina, and in retinal pigment epithelium, while VDR epitopes have also been found in the ciliary body epithelium, pointing to the role of this protein in eye physiology. The 1,25(OH)2D3 modulates expression of the genes involved in the regulation of intraocular pressure in non-human primates. Extracellular matrix can be remodeled by 1,25(OH)2D3 treatment. Actin disruption can lead to cell morphology alteration, trabecular meshwork relaxation and intraocular pressure reduction. This observational cross-sectional study included 90 female glaucoma subjects aged 45-55 and 50 glaucoma free female subjects as control group. Results of a pilot study conducted in 20 glaucoma subjects and 20 control subjects are presented below. All study subjects underwent history taking, complete ophthalmologic examination and serum vitamin D determination. The mean serum vitamin D level was 32.31 nmol/L in glaucoma patients and 64.17 nmol/L in control subjects. Serum vitamin D level was statistically significantly lower in glaucoma patients as compared with control group (p<0.05).Cilj istraživanja bio je utvrditi je li kod ispitanica oboljelih od glaukoma snižena serumska koncentracija vitamina D u odnosu na kontrolnu skupinu. Mehanizam kojim vitamin D snižava očni tlak nije jasno poznat. Gotovo sva tkiva posjeduju receptor za vitamin D (VDR). Velik doprinos razumijevanju globalne fiziološke funkcije vitamina D dobiven je od miša kojemu nedostaje VDR (engl. knockout mice for VDR). VDR je pronađen u nekim stanicama ganglijskog sloja, u vanjskom i unutarnjem nuklearnom sloju mrežnice i u retinalnom pigmentnom epitelu. Epitopi za VDR su pronađeni i u epitelu cilijarnog tijela. To sve govori o važnosti tog proteina u fiziologiji oka. 1,25 (OH)2D3 modulira ekspresiju gena koji su uključeni u regulaciju očnog tlaka u nehumanih primata. Nakon liječenja pomoću 1,25(OH)2D3 može se remodelirati ekstracelularni matriks. Disrupcija aktina može dovesti do promjene stanične morfologije, relaksacije trabekularne mreže i sniženja očnog tlaka. Provedeno je opažajno presječno istraživanje s kontrolnom skupinom. U istraživanje je bilo uključeno 90 ispitanica oboljelih od glaukoma u dobi od 45-55 godina i 50 ispitanica u kontrolnoj skupini. Prikazuju se rezultati probnog ispitivanja u 20 ispitanica oboljelih od glaukoma i isto toliko u kontrolnoj skupini. Ispitanicama je uzeta anamneza i kompletan oftalmološki status te je određen vitamin D u serumu. Koncentracija vitamina D u serumu ispitanica s glaukomom bila je 32,31 nmol/L u odnosu na kontrolnu skupinu gdje je bila 64,17 nmol/L. U zaključku, kod ispitanica oboljelih od glaukoma bila je snižena serumska koncentracija vitamina D u odnosu na kontrolnu skupinu na statistički značajnoj razini od p<0,05

Microincision Aponeurotic Ptosis Surgery of Upper Lid

The paper is a prospective study of 23 lids of 20 patients with upper lid aponeurotic ptosis operated using microincision technique in period 2005-2008. There were 7 males and 13 females. Age of the patients was 28–83 years (y), average 61±17 y, for female 63±13.4 y and for male 61±19 y. Inclusion criteria were: aponeurotic upper lid ptosis more than 2 mm, no other lid abnormalities, minimal dermatochalasis, no previous or concomitant lid surgery. The procedure was performed in local anesthesia through 10 mm cut. Aponeurosis was fixated to the tarsal plate with two sutures. Success was considered if operated lid height differed up to 0.5 mm of the other eye and margin-to-reflex distance was 2–4 mm in primary position. Postoperative results regarding contour, skin crease and lash position were good in all patients. Regarding height, 19/23 (83%) met criteria of 0.5 mm of the other eye and MRD 2–4 mm. In one bilateral procedure there was an asymmetry of 1 mm. Three patients with unilateral procedure had at least 1mm asymmetry comparing to the other eye. Reoperation was neccessary in two bilateral cases. Lid fold was symmetrical only in 7 patients (35%). The rest had slight to grose lid fold asymmetry. Complications were scarce, in early postoperative period there was hematoma in two patients lasting up to three weeks. Late failure was noticed in two cases 6 and 8 months postoperatively. Advantages are: less anesthetic results in less decreased levator function and more accurate assessment of eyelid position intraoperatively, less distortion of the lid due to less bleeding and edema, shorter operation time, less scarring and shortened recovery time. However it can be used only in selective cases

Prediction of corneal graft reaction/rejection due to preoperative measurement of vascular endothelial growth factor in recipient cornea

Transplantacija rožnice se danas smatra najizvođenijom i najuspješnijom trasnplantacijskom procedurom, s postotkom usješnost do 90%. Uspjeh keratoplastike kod rožnica s neovaskularizacijom smanjuje uspjeh keratoplastike na 40% prvi prvoj keratoplastici, pri ponovljenim i više. Istraživanja ukazuju da je vaskularni endotelni čimbenik rasta jedan od glavnih induktora angiogeneze, vaskulogeneze, te limfogeneze i u normalnim i u patološkim stanjima kako u raznim organima, tako i u rožnici. Prethodnim istraživanjem utvrdili smo povezanost VEGF u normalnoj i patološkoj rožnici, a u ovom istraživanju postavljeni su sljedeći ciljevi: 1. Odrediti količinu VEGF-a metodom ELISE u patološkim rožnicama bolesnika koji su operirani perforativnom keratoplastikom (transplantacija rožnice), međusobno ih usporediti te ih usporediti sa zdravim rožnicama kadavera. 2. Odrediti mjesto proizvodnje VEGF-a metodom imunohistokemije na patološkim rožnicama u bolesnika koji su operirani perforativnom keratoplastikom (transplantacija rožnice), međusobno ih usporediti te ih usporediti sa zdravim rožnicama kadavera. 3. Usporediti postoji li korelacija količina te mjesta nastanka VEGF-a s postoperativnim znakovima odbacivanja transplantata. U istraživanje je bilo uključeno 25 bolesnika koji su hospitalizirani radi operacije perforativne keratoplastike na Klinici za očne bolesti, Kliničke bolnice „Sveti Duh“ Zagreb u razdoblju od 15. 10. 2006. do 15. 3. 2007. Predoperativno su bolesnici pregledani radi evaluacije uzroka bolesti rožnice i vidnih funkcija bolesnika. Bolesnici su podijeljeni u tri skupine prigodom pregleda rožnice na bimikroskopu predoperativno: upalni s neoveovaskularizacijama, upalni bez neovaskularizacije, neupalni. Prema intraoperativnom postupku, rožnica se razrezala na dvije jednake polovine. Jedna polovina se odmah uronila u 4% puferirani formalin i poslala na Zavod za patologiju, Opće bolnice „Dr. Josip Benčević“, Slavonski Brod gdje su uzorci uklopljeni u parafinske blokove, rezani na rezove debljine 3 µm. Nakon toga učinila se imunohistokemija uzoraka. Druga polovina stavila se u 0,5 ml medija za pohranu (Cornea Max®, Eurobio, France) te analizirala komercijalnim ELISA testom u Institutu „Ruđer Bošković“, Zagreb. Postoperativno su bolesnici praćeni kroz tri godine radi praćenja znakova odbacivanja transplantata i vidnih funkcija bolesnika. U istraživanje je bilo uključeno i 25 rožnica kadavera koji predstavljaju kontrolnu skupinu. Rožnice su uzete od bolesnika preminulih u Općoj bolnici „Dr. Josip Benčević“ u Slavonskom Brodu u postmortem razdoblju od maksimalno 24 sata. Također su analizirane donorske rožnice i to se predoperativno mjerio broj endotelnih stanica spekularnim mikroskopom. Postoperativno praćenje bolesnika trajala je od listopada 2006. do ožujka 2010., a ispitivale su se iste vidne funkcije bolesnika kao u predoperativnom pregledu i tražili su se znakovi odbacivanja transplantata rožnice ili stanje odbačenog transplantata. Statističkom analizom vidi se trend da su operirani bolesnici imali u prosjeku višu vrijednost VEGF-a (M = 222,6; SD = 129,834) od kontrolne skupine (M = 142,3; SD = 93,081). Nije postojala statistički važna razlika u mjestu proizvodnje VEGF-a između bolesnika i kontrolne skupine. Povezanost reakcije odbacivanja i konačnog odbacivanja rožnice bila je statistički važna, što znači da su oni bolesnici koji su imali reakciju odbacivanja ujedno i u većoj mjeri i konačno odbacili transplantant (Fi = 0,618; p < 0,01). Reakciju odbacivanja/odbacivanje transplantanta u najvećoj mjeri su imali bolesnici u prvoj skupini, odnosno oni s dijagnozom upalnih promjena s neovaskularizacijama. Post hoc testiranje Bonferroni testom pokazalo je kako statistički znatne razlike postoje između skupine bolesnika s upalnim promjenama s neovaskularizacijama i skupine bolesnika koji su imali neupalne promjene te kontrolne skupine (na razini od 5%; p < 0,05). Bolesnici koji su imali reakciju odbacivanja su, u prosjeku imali i veću razinu VEGF-a (307,4 nasuprot 182,8). Bolesnici koji su odbacili transplantant također su imali višu razinu VEGF-a od bolesnika koji nisu odbacili transplantant (344,3 nasuprot 184,2). Razina VEGF-a nije bila povezana s kratkotrajnim i dugoročnim komplikacijama. Nije postojala statistički važna povezanost reakcija odbacivanja transplantanta, stvarnog odbacivanja te kratkoročnih i dugoročnih komplikacija s mjestom proizvodnje VEGF-a. Dobiven je trend da se odbacivanje transplantanta javilo samo kod bolesnika kod kojih se VEGF proizvodio u endotelu, odnosno u više slojeva. Dobiveni rezultati ukazuju da bolesnici koji imaju više razine VEGF-a u rožnicama podvrgnutim perforativnoj keratoplastici imaju češće reakciju odbacivanja transplantanta te konačno odbacivanje transplantanta. Ono što se pokazalo je da se količina VEGF-a, u skupini s upalnim promjenama bez neovaskularizacije, ne razlikuje statistički znatno od količine kod skupine bolesnika s upalnim promjenama s neovaskularizacijama, ali niti od skupine bolesnika s neupalnim promjenama i kontrolne skupine. To govori u prilog saznanju da klinički pregled sam nije dovoljan da predviđa razinu VEGF-a i s time povezano reakciju odbacivanja transplantata. Mjesta proizvodnje VEGF-a odgovaraju svim slojevima rožnice kao što je dokazano u literaturi, ali nije specifično za skupinu bolesnika, komplikacije i znakove reakcije odbacivanja.Purpose: Monitoring the clinical course of corneal grafts in terms of preoperative measurements of vascular endothelial growth factor (VEGF) in the donor cornea so as to estimate the probability of graft reaction and graft rejection. ----- Methods: The study included 25 patients hospitalised in order to undergo penetrative keratoplasty. The patients underwent preoperative examination so as to determine the causes of corneal diseases and the visual functions of patients. The patients were divided into three groups after the preoperative corneal examination using a slit lamp: inflammatory with neovascularisations, inflammatory with no neovascularisations, and non-inflammatory. Following the intraoperative procedure, corneas were cut into two equal halves. One half was analysed using a commercial enzyme-linked immunosorbent assay (ELISA) and the amount of VEGF was determined, and the other half was analysed using the immunohistochemistry method so as to determine the locus of VEGF production qualitatively. The postoperative patient follow-up lasted 3 years in order to monitor the symptoms of graft rejection and the patients' visual functions. The study also included 25 cadaver corneas which represented the control group. ----- Results: Statistical analysis shows a trend where the patients who were operated on exhibited higher VEGF values (M=222.6 pg/ml; SD=129.834) than the control group (M=142.3pg/ml; SD=93.081). There was no statistically significant difference in the locus of VEGF production between the patients and the control group. Graft reaction and graft rejection were largely present in the first group of patients diagnosed with inflammatory changes with neovascularisations. Post-hoc tests using the Bonferroni test showed that there were statistically significant differences between the group of patients with inflammatory changes with neovascularisations, the group of patients with non-inflammatory changes, and the control group (p<0.05). On average, patients with graft reaction had a higher level of VEGF (307.4 pg/ml in contrast with 182.8 pg/ml). Patients with graft rejection also had higher VEGF levels than the patients with no graft rejection (344.3 pg/ml in contrast with 184.2 pg/ml). There was no statistically significant link between graft reaction and graft rejection and the locus of VEGF production. ----- Conclusion: The results suggest that graft reaction and graft rejection are more often in patients with higher levels of VEGF in corneas subjected to penetrating keratoplasty

Prediction of corneal graft reaction/rejection due to preoperative measurement of vascular endothelial growth factor in recipient cornea

Transplantacija rožnice se danas smatra najizvođenijom i najuspješnijom trasnplantacijskom procedurom, s postotkom usješnost do 90%. Uspjeh keratoplastike kod rožnica s neovaskularizacijom smanjuje uspjeh keratoplastike na 40% prvi prvoj keratoplastici, pri ponovljenim i više. Istraživanja ukazuju da je vaskularni endotelni čimbenik rasta jedan od glavnih induktora angiogeneze, vaskulogeneze, te limfogeneze i u normalnim i u patološkim stanjima kako u raznim organima, tako i u rožnici. Prethodnim istraživanjem utvrdili smo povezanost VEGF u normalnoj i patološkoj rožnici, a u ovom istraživanju postavljeni su sljedeći ciljevi: 1. Odrediti količinu VEGF-a metodom ELISE u patološkim rožnicama bolesnika koji su operirani perforativnom keratoplastikom (transplantacija rožnice), međusobno ih usporediti te ih usporediti sa zdravim rožnicama kadavera. 2. Odrediti mjesto proizvodnje VEGF-a metodom imunohistokemije na patološkim rožnicama u bolesnika koji su operirani perforativnom keratoplastikom (transplantacija rožnice), međusobno ih usporediti te ih usporediti sa zdravim rožnicama kadavera. 3. Usporediti postoji li korelacija količina te mjesta nastanka VEGF-a s postoperativnim znakovima odbacivanja transplantata. U istraživanje je bilo uključeno 25 bolesnika koji su hospitalizirani radi operacije perforativne keratoplastike na Klinici za očne bolesti, Kliničke bolnice „Sveti Duh“ Zagreb u razdoblju od 15. 10. 2006. do 15. 3. 2007. Predoperativno su bolesnici pregledani radi evaluacije uzroka bolesti rožnice i vidnih funkcija bolesnika. Bolesnici su podijeljeni u tri skupine prigodom pregleda rožnice na bimikroskopu predoperativno: upalni s neoveovaskularizacijama, upalni bez neovaskularizacije, neupalni. Prema intraoperativnom postupku, rožnica se razrezala na dvije jednake polovine. Jedna polovina se odmah uronila u 4% puferirani formalin i poslala na Zavod za patologiju, Opće bolnice „Dr. Josip Benčević“, Slavonski Brod gdje su uzorci uklopljeni u parafinske blokove, rezani na rezove debljine 3 µm. Nakon toga učinila se imunohistokemija uzoraka. Druga polovina stavila se u 0,5 ml medija za pohranu (Cornea Max®, Eurobio, France) te analizirala komercijalnim ELISA testom u Institutu „Ruđer Bošković“, Zagreb. Postoperativno su bolesnici praćeni kroz tri godine radi praćenja znakova odbacivanja transplantata i vidnih funkcija bolesnika. U istraživanje je bilo uključeno i 25 rožnica kadavera koji predstavljaju kontrolnu skupinu. Rožnice su uzete od bolesnika preminulih u Općoj bolnici „Dr. Josip Benčević“ u Slavonskom Brodu u postmortem razdoblju od maksimalno 24 sata. Također su analizirane donorske rožnice i to se predoperativno mjerio broj endotelnih stanica spekularnim mikroskopom. Postoperativno praćenje bolesnika trajala je od listopada 2006. do ožujka 2010., a ispitivale su se iste vidne funkcije bolesnika kao u predoperativnom pregledu i tražili su se znakovi odbacivanja transplantata rožnice ili stanje odbačenog transplantata. Statističkom analizom vidi se trend da su operirani bolesnici imali u prosjeku višu vrijednost VEGF-a (M = 222,6; SD = 129,834) od kontrolne skupine (M = 142,3; SD = 93,081). Nije postojala statistički važna razlika u mjestu proizvodnje VEGF-a između bolesnika i kontrolne skupine. Povezanost reakcije odbacivanja i konačnog odbacivanja rožnice bila je statistički važna, što znači da su oni bolesnici koji su imali reakciju odbacivanja ujedno i u većoj mjeri i konačno odbacili transplantant (Fi = 0,618; p < 0,01). Reakciju odbacivanja/odbacivanje transplantanta u najvećoj mjeri su imali bolesnici u prvoj skupini, odnosno oni s dijagnozom upalnih promjena s neovaskularizacijama. Post hoc testiranje Bonferroni testom pokazalo je kako statistički znatne razlike postoje između skupine bolesnika s upalnim promjenama s neovaskularizacijama i skupine bolesnika koji su imali neupalne promjene te kontrolne skupine (na razini od 5%; p < 0,05). Bolesnici koji su imali reakciju odbacivanja su, u prosjeku imali i veću razinu VEGF-a (307,4 nasuprot 182,8). Bolesnici koji su odbacili transplantant također su imali višu razinu VEGF-a od bolesnika koji nisu odbacili transplantant (344,3 nasuprot 184,2). Razina VEGF-a nije bila povezana s kratkotrajnim i dugoročnim komplikacijama. Nije postojala statistički važna povezanost reakcija odbacivanja transplantanta, stvarnog odbacivanja te kratkoročnih i dugoročnih komplikacija s mjestom proizvodnje VEGF-a. Dobiven je trend da se odbacivanje transplantanta javilo samo kod bolesnika kod kojih se VEGF proizvodio u endotelu, odnosno u više slojeva. Dobiveni rezultati ukazuju da bolesnici koji imaju više razine VEGF-a u rožnicama podvrgnutim perforativnoj keratoplastici imaju češće reakciju odbacivanja transplantanta te konačno odbacivanje transplantanta. Ono što se pokazalo je da se količina VEGF-a, u skupini s upalnim promjenama bez neovaskularizacije, ne razlikuje statistički znatno od količine kod skupine bolesnika s upalnim promjenama s neovaskularizacijama, ali niti od skupine bolesnika s neupalnim promjenama i kontrolne skupine. To govori u prilog saznanju da klinički pregled sam nije dovoljan da predviđa razinu VEGF-a i s time povezano reakciju odbacivanja transplantata. Mjesta proizvodnje VEGF-a odgovaraju svim slojevima rožnice kao što je dokazano u literaturi, ali nije specifično za skupinu bolesnika, komplikacije i znakove reakcije odbacivanja.Purpose: Monitoring the clinical course of corneal grafts in terms of preoperative measurements of vascular endothelial growth factor (VEGF) in the donor cornea so as to estimate the probability of graft reaction and graft rejection. ----- Methods: The study included 25 patients hospitalised in order to undergo penetrative keratoplasty. The patients underwent preoperative examination so as to determine the causes of corneal diseases and the visual functions of patients. The patients were divided into three groups after the preoperative corneal examination using a slit lamp: inflammatory with neovascularisations, inflammatory with no neovascularisations, and non-inflammatory. Following the intraoperative procedure, corneas were cut into two equal halves. One half was analysed using a commercial enzyme-linked immunosorbent assay (ELISA) and the amount of VEGF was determined, and the other half was analysed using the immunohistochemistry method so as to determine the locus of VEGF production qualitatively. The postoperative patient follow-up lasted 3 years in order to monitor the symptoms of graft rejection and the patients' visual functions. The study also included 25 cadaver corneas which represented the control group. ----- Results: Statistical analysis shows a trend where the patients who were operated on exhibited higher VEGF values (M=222.6 pg/ml; SD=129.834) than the control group (M=142.3pg/ml; SD=93.081). There was no statistically significant difference in the locus of VEGF production between the patients and the control group. Graft reaction and graft rejection were largely present in the first group of patients diagnosed with inflammatory changes with neovascularisations. Post-hoc tests using the Bonferroni test showed that there were statistically significant differences between the group of patients with inflammatory changes with neovascularisations, the group of patients with non-inflammatory changes, and the control group (p<0.05). On average, patients with graft reaction had a higher level of VEGF (307.4 pg/ml in contrast with 182.8 pg/ml). Patients with graft rejection also had higher VEGF levels than the patients with no graft rejection (344.3 pg/ml in contrast with 184.2 pg/ml). There was no statistically significant link between graft reaction and graft rejection and the locus of VEGF production. ----- Conclusion: The results suggest that graft reaction and graft rejection are more often in patients with higher levels of VEGF in corneas subjected to penetrating keratoplasty

Utjecaj vaskularnog endotelnog čimbenika rasta na odbacivanje transplantata ljudske rožnice [Prediction of corneal graft reaction/rejection due to preoperative measurement of vascular endothelial growth factor in recipient cornea]

Purpose: Monitoring the clinical course of corneal grafts in terms of preoperative measurements of vascular endothelial growth factor (VEGF) in the donor cornea so as to estimate the probability of graft reaction and graft rejection. ----- Methods: The study included 25 patients hospitalised in order to undergo penetrative keratoplasty. The patients underwent preoperative examination so as to determine the causes of corneal diseases and the visual functions of patients. The patients were divided into three groups after the preoperative corneal examination using a slit lamp: inflammatory with neovascularisations, inflammatory with no neovascularisations, and non-inflammatory. Following the intraoperative procedure, corneas were cut into two equal halves. One half was analysed using a commercial enzyme-linked immunosorbent assay (ELISA) and the amount of VEGF was determined, and the other half was analysed using the immunohistochemistry method so as to determine the locus of VEGF production qualitatively. The postoperative patient follow-up lasted 3 years in order to monitor the symptoms of graft rejection and the patients' visual functions. The study also included 25 cadaver corneas which represented the control group. ----- Results: Statistical analysis shows a trend where the patients who were operated on exhibited higher VEGF values (M=222.6 pg/ml; SD=129.834) than the control group (M=142.3pg/ml; SD=93.081). There was no statistically significant difference in the locus of VEGF production between the patients and the control group. Graft reaction and graft rejection were largely present in the first group of patients diagnosed with inflammatory changes with neovascularisations. Post-hoc tests using the Bonferroni test showed that there were statistically significant differences between the group of patients with inflammatory changes with neovascularisations, the group of patients with non-inflammatory changes, and the control group (p<0.05). On average, patients with graft reaction had a higher level of VEGF (307.4 pg/ml in contrast with 182.8 pg/ml). Patients with graft rejection also had higher VEGF levels than the patients with no graft rejection (344.3 pg/ml in contrast with 184.2 pg/ml). There was no statistically significant link between graft reaction and graft rejection and the locus of VEGF production. ----- Conclusion: The results suggest that graft reaction and graft rejection are more often in patients with higher levels of VEGF in corneas subjected to penetrating keratoplasty

Prediction of corneal graft reaction/rejection due to preoperative measurement of vascular endothelial growth factor in recipient cornea

Transplantacija rožnice se danas smatra najizvođenijom i najuspješnijom trasnplantacijskom procedurom, s postotkom usješnost do 90%. Uspjeh keratoplastike kod rožnica s neovaskularizacijom smanjuje uspjeh keratoplastike na 40% prvi prvoj keratoplastici, pri ponovljenim i više. Istraživanja ukazuju da je vaskularni endotelni čimbenik rasta jedan od glavnih induktora angiogeneze, vaskulogeneze, te limfogeneze i u normalnim i u patološkim stanjima kako u raznim organima, tako i u rožnici. Prethodnim istraživanjem utvrdili smo povezanost VEGF u normalnoj i patološkoj rožnici, a u ovom istraživanju postavljeni su sljedeći ciljevi: 1. Odrediti količinu VEGF-a metodom ELISE u patološkim rožnicama bolesnika koji su operirani perforativnom keratoplastikom (transplantacija rožnice), međusobno ih usporediti te ih usporediti sa zdravim rožnicama kadavera. 2. Odrediti mjesto proizvodnje VEGF-a metodom imunohistokemije na patološkim rožnicama u bolesnika koji su operirani perforativnom keratoplastikom (transplantacija rožnice), međusobno ih usporediti te ih usporediti sa zdravim rožnicama kadavera. 3. Usporediti postoji li korelacija količina te mjesta nastanka VEGF-a s postoperativnim znakovima odbacivanja transplantata. U istraživanje je bilo uključeno 25 bolesnika koji su hospitalizirani radi operacije perforativne keratoplastike na Klinici za očne bolesti, Kliničke bolnice „Sveti Duh“ Zagreb u razdoblju od 15. 10. 2006. do 15. 3. 2007. Predoperativno su bolesnici pregledani radi evaluacije uzroka bolesti rožnice i vidnih funkcija bolesnika. Bolesnici su podijeljeni u tri skupine prigodom pregleda rožnice na bimikroskopu predoperativno: upalni s neoveovaskularizacijama, upalni bez neovaskularizacije, neupalni. Prema intraoperativnom postupku, rožnica se razrezala na dvije jednake polovine. Jedna polovina se odmah uronila u 4% puferirani formalin i poslala na Zavod za patologiju, Opće bolnice „Dr. Josip Benčević“, Slavonski Brod gdje su uzorci uklopljeni u parafinske blokove, rezani na rezove debljine 3 µm. Nakon toga učinila se imunohistokemija uzoraka. Druga polovina stavila se u 0,5 ml medija za pohranu (Cornea Max®, Eurobio, France) te analizirala komercijalnim ELISA testom u Institutu „Ruđer Bošković“, Zagreb. Postoperativno su bolesnici praćeni kroz tri godine radi praćenja znakova odbacivanja transplantata i vidnih funkcija bolesnika. U istraživanje je bilo uključeno i 25 rožnica kadavera koji predstavljaju kontrolnu skupinu. Rožnice su uzete od bolesnika preminulih u Općoj bolnici „Dr. Josip Benčević“ u Slavonskom Brodu u postmortem razdoblju od maksimalno 24 sata. Također su analizirane donorske rožnice i to se predoperativno mjerio broj endotelnih stanica spekularnim mikroskopom. Postoperativno praćenje bolesnika trajala je od listopada 2006. do ožujka 2010., a ispitivale su se iste vidne funkcije bolesnika kao u predoperativnom pregledu i tražili su se znakovi odbacivanja transplantata rožnice ili stanje odbačenog transplantata. Statističkom analizom vidi se trend da su operirani bolesnici imali u prosjeku višu vrijednost VEGF-a (M = 222,6; SD = 129,834) od kontrolne skupine (M = 142,3; SD = 93,081). Nije postojala statistički važna razlika u mjestu proizvodnje VEGF-a između bolesnika i kontrolne skupine. Povezanost reakcije odbacivanja i konačnog odbacivanja rožnice bila je statistički važna, što znači da su oni bolesnici koji su imali reakciju odbacivanja ujedno i u većoj mjeri i konačno odbacili transplantant (Fi = 0,618; p < 0,01). Reakciju odbacivanja/odbacivanje transplantanta u najvećoj mjeri su imali bolesnici u prvoj skupini, odnosno oni s dijagnozom upalnih promjena s neovaskularizacijama. Post hoc testiranje Bonferroni testom pokazalo je kako statistički znatne razlike postoje između skupine bolesnika s upalnim promjenama s neovaskularizacijama i skupine bolesnika koji su imali neupalne promjene te kontrolne skupine (na razini od 5%; p < 0,05). Bolesnici koji su imali reakciju odbacivanja su, u prosjeku imali i veću razinu VEGF-a (307,4 nasuprot 182,8). Bolesnici koji su odbacili transplantant također su imali višu razinu VEGF-a od bolesnika koji nisu odbacili transplantant (344,3 nasuprot 184,2). Razina VEGF-a nije bila povezana s kratkotrajnim i dugoročnim komplikacijama. Nije postojala statistički važna povezanost reakcija odbacivanja transplantanta, stvarnog odbacivanja te kratkoročnih i dugoročnih komplikacija s mjestom proizvodnje VEGF-a. Dobiven je trend da se odbacivanje transplantanta javilo samo kod bolesnika kod kojih se VEGF proizvodio u endotelu, odnosno u više slojeva. Dobiveni rezultati ukazuju da bolesnici koji imaju više razine VEGF-a u rožnicama podvrgnutim perforativnoj keratoplastici imaju češće reakciju odbacivanja transplantanta te konačno odbacivanje transplantanta. Ono što se pokazalo je da se količina VEGF-a, u skupini s upalnim promjenama bez neovaskularizacije, ne razlikuje statistički znatno od količine kod skupine bolesnika s upalnim promjenama s neovaskularizacijama, ali niti od skupine bolesnika s neupalnim promjenama i kontrolne skupine. To govori u prilog saznanju da klinički pregled sam nije dovoljan da predviđa razinu VEGF-a i s time povezano reakciju odbacivanja transplantata. Mjesta proizvodnje VEGF-a odgovaraju svim slojevima rožnice kao što je dokazano u literaturi, ali nije specifično za skupinu bolesnika, komplikacije i znakove reakcije odbacivanja.Purpose: Monitoring the clinical course of corneal grafts in terms of preoperative measurements of vascular endothelial growth factor (VEGF) in the donor cornea so as to estimate the probability of graft reaction and graft rejection. ----- Methods: The study included 25 patients hospitalised in order to undergo penetrative keratoplasty. The patients underwent preoperative examination so as to determine the causes of corneal diseases and the visual functions of patients. The patients were divided into three groups after the preoperative corneal examination using a slit lamp: inflammatory with neovascularisations, inflammatory with no neovascularisations, and non-inflammatory. Following the intraoperative procedure, corneas were cut into two equal halves. One half was analysed using a commercial enzyme-linked immunosorbent assay (ELISA) and the amount of VEGF was determined, and the other half was analysed using the immunohistochemistry method so as to determine the locus of VEGF production qualitatively. The postoperative patient follow-up lasted 3 years in order to monitor the symptoms of graft rejection and the patients' visual functions. The study also included 25 cadaver corneas which represented the control group. ----- Results: Statistical analysis shows a trend where the patients who were operated on exhibited higher VEGF values (M=222.6 pg/ml; SD=129.834) than the control group (M=142.3pg/ml; SD=93.081). There was no statistically significant difference in the locus of VEGF production between the patients and the control group. Graft reaction and graft rejection were largely present in the first group of patients diagnosed with inflammatory changes with neovascularisations. Post-hoc tests using the Bonferroni test showed that there were statistically significant differences between the group of patients with inflammatory changes with neovascularisations, the group of patients with non-inflammatory changes, and the control group (p<0.05). On average, patients with graft reaction had a higher level of VEGF (307.4 pg/ml in contrast with 182.8 pg/ml). Patients with graft rejection also had higher VEGF levels than the patients with no graft rejection (344.3 pg/ml in contrast with 184.2 pg/ml). There was no statistically significant link between graft reaction and graft rejection and the locus of VEGF production. ----- Conclusion: The results suggest that graft reaction and graft rejection are more often in patients with higher levels of VEGF in corneas subjected to penetrating keratoplasty