[Allergic and immunopathological diseases of the ocular surface]. / A szemfelszín allergiás és immunpatológiai betegségei.

Allergic and immunopathological diseases of the ocular surface are inflammations that can occur with mild to severe symptoms that cause visual impairment. Allergic inflammations mainly affect the conjunctiva, causing acute and/or chronic conjunctivitis. Several forms are distinguished: seasonal allergic conjunctivitis, vernal conjunctivitis, atopic keratoconjunctivitis, contact allergy, giant papillary conjunctivitis. The most common is the seasonal form, which is linked to seasons. Allergic ocular surface processes require local treatment with artificial tears, anti-allergic eye drops. If complications occur, topical corticosteroid and cyclosporin treatment may be used. Immunopathological inflammations of the ocular surface are associated with systemic diseases. Keratoconjunctivitis sicca, although occurring in the absence of systemic disease, is a common companion of Sjögren's syndrome and collagen diseases. Ocular pemphigoid belongs to the group of mucous membrane pemphigoids. After the initial conjunctivitis symptoms, subconjunctival fibrosis begins, leading to the development of sym- and ankyloblepharon. In the final stage, the ocular surface is covered by scar tissue (ocular cicatricial pemphigoid) which practically results in loss of vision. Peripheral ulcerative keratitis is usually associated with collagen vascular disease, rheumatoid arthritis. A 3-4 mm long, curved infiltration starting near the limbus becomes ulcerated and then perforates, on which the iris may prolapse. First, systemic treatment is required, which is an interdisciplinary task. Topical corticosteroid and cyclosporine eye drops may be administered. In the case of corneal perforation, amniotic membrane transplantation and/or keratoplasty may be performed. Orv Hetil. 2023; 164(43): 1686-1692.

The inheritance of corneal endothelial cell density.

BACKGROUND: Although it is known that some corneal diseases and degenerations have a significant heritable background, heritability on corneal endothelial cell density (ECD) has never been clearly determined. Our aim was to determine the heritability of corneal ECD. MATERIAL AND METHODS: Corneal ECD of 114 eyes (66 eyes of 33 monozygotic and 48 eyes of 24 dizygotic pairs; mean age 49.0 ± 15.5 years) was investigated by Konan Noncon Robo NSP-9900 specular microscopy. Structural equation modeling (ACE model) was applied. RESULTS: Endothelial corneal cell density was highly heritable (82.0%, 95%CI, 70.0-92.0%), whereas the unique environmental contribution was 18.0% (95%CI, 8.0-29.0%). Shared environmental factors had no influence on the endothelial corneal cell density. DISCUSSION: In this twin study, we established first that the density of the corneal endothelial cells is strongly heritable, which should stimulate future genetic studies to identify genes and pathways that are involved in determining ECD which might in turn lead to future treatments to prevent EC loss.

Genetic covariance between central corneal thickness and anterior chamber volume: a Hungarian twin study.

BACKGROUND: Few, and inconsistent, studies have showed high heritability of some parameters of the anterior segment of the eye; however, no heritability of anterior chamber volume (ACV) has been reported, and no study has been performed to investigate the correlation between the ACV and central corneal thickness (CCT). METHODS: Anterior segment measurements (Pentacam, Oculus) were obtained from 220 eyes of 110 adult Hungarian twins (41 monozygotic and 14 same-sex dizygotic pairs; 80% women; age 48.6 ± 15.5 years) obtained from the Hungarian Twin Registry. RESULTS: Age- and sex-adjusted heritability of ACV was 85% (bootstrapped 95% confidence interval; CI: 69% to 93%), and 88% for CCT (CI: 79% to 95%). Common environmental effects had no influence, and unshared environmental factors were responsible for 12% and 15% of the variance, respectively. The correlation between ACV and CCT was negative and significant (r ph = -0.35, p < .05), and genetic factors accounted for the covariance significantly (0.934; CI: 0.418, 1.061) based on the bivariate Cholesky decomposition model. CONCLUSION: These findings support the high heritability of ACV and central corneal thickness, and a strong genetic covariance between them, which underscores the importance of identification of the specific genetic factors and the family risk-based screening of disorders related to these variables, such as open-angle and also angle closure glaucoma and corneal endothelial alterations.

[Postoperative therapy after penetrating keratoplasty in herpes simplex keratitis]. / Herpes simplex keratitisekben végzett perforáló keratoplasztika posztoperatív terápiája.

INTRODUCTION: Keratitis due to herpes simplex infection is a common cause of corneal damage resulting in impaired vision. AIM: The aim of this study was to assess the outcome of penetrating keratoplasties in patients treated with systemic antiviral and immunosuppressive drugs. METHOD: The authors retrospectively analysed data of 12 patients who underwent penetrating keratoplasty. The average age at onset of the first keratitis preceding surgery was 18 years (between 5 and 40 years). The indication for surgery in 9 cases was to improve vision and in 3 patient to prevent corneal perforation. Nine patients were given both acyclovir and mycophenolate mofetil, as anti-viral agent and immunosuppressive treatment, respectively. Two patients were treated with anti-viral agent only while one patient received no systemic therapy. The average follow-up time was 53.1 months (between 16 and 84 months). RESULTS: Of the 9 patients who underwent surgery for improving vision, 8 patients had transparent grafts during follow up without vascularization. All eight patients had been treated with acyclovir and mycophenolate mofetil. In one patient who had no systemic treatment recurrence and graft rejection was observed. Only one of the surgeries performed in acute stage of inflammation resulted in a properly healed transparent graft without recurrence and rejection. In this patient acyclivir and mycophenolate mofetil therapy had been given previously. In two cases the preventive - full or partial - systemic treatment had no effect. The visual acuity improved in all cases. In three patients visual acuity was influenced by some other factors as well. CONCLUSIONS: The systemic acyclovir and mycophenolat mofetil therapy is fairly successful in perforating keratoplasty due to herpes simplex infection. Acyclovir decreases the risk of recurrence, while mycophenolate mofetil may prevent graft rejection. The timing of surgery is decisive; it leads to better results when performed in a scarred, noninflammatory state.

[Hypertension-related eye disorders]. / A magas vérnyomás szemészeti következményei.

Hypertension affects a significant proportion of the population, however, it is often diagnosed with a delay. The aim of this article is to review the well known and less known eye abnormalities related to hypertension, and place them in the context of population based studies. Hypertension affects various parts of the eye. The originally classified hypertensive retinopathy (retinal microvascular changes) is still relevant, but new features are visible in cases of controlled hypertension. Signs of mild hypertensive retinopathy are more common than expected occurring in nearly 10-15% of the adult non-diabetic population. Hypertensive retinopathy can be an indicator of other hypertensive complications such as neurologic and cardiac complications. Microvascular changes are reversible in well controlled hypertension. Proper treatment of hypertension can reduce the development and progression of diabetic retinopathy and, thus, visual loss due to severe retinal diseases such as retinal vascular occlusion (artery and vein), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration.

Complement activation in the aqueous humor of pseudophakic bullous keratopathy patients.

BACKGROUND/AIMS: According to some studies, inflammation is a potential etiological factor in pseudophakic bullous keratopathy (PBK). Our aim was to obtain information on the activation of the complement system in the aqueous humor in this disorder. METHODS: Aqueous humor samples were collected during keratoplasty of 12 PBK patients, as well as during phacoemulsification surgery of 18 control patients. The concentrations of the protein-protein complexes generated during complement activation (C1rC1sC1inh and C3bBbP) through the classical and alternative pathways, respectively, as well as of the C3 cleavage product C3a, were measured with ELISA methods. The correlation among the complement factors and between the duration of the edema, the stage of the disease, and the level of the complement activation products was examined. RESULTS: The concentration of C1rC1sC1inh, C3bBbP complex and C3a was significantly higher in the PBK group (p < 0.001) compared to the control group. In PBK patients, a correlation was found between the levels of the C1rC1sC1inh complex and C3a only. CONCLUSION: Our new findings indicate that in PBK the complement system is activated - via the classical pathway - in the aqueous humor. The activated complement may play a role in increased endothelial cell loss.

Positioning of electronic subretinal implants in blind retinitis pigmentosa patients through multimodal assessment of retinal structures.

PURPOSE: To optimize methods for positioning subretinal visual implants, customizing their cable length, guiding them to the predetermined retinal position, and evaluating their performance. METHODS: Ten eyes of 10 patients (6 male, 4 female, mean age 46.4 years) were investigated before implantation of a subretinal visual implant. The structural characteristics of the retina as well as the ocular dimensions were determined. Topographic images of the prospective implantation site were subdivided into grids of squares. Each square received a weighted score for suitability. The sum of the scores was calculated, and the region with the highest score was chosen for the implant. In each case, the implant's power supply cable length was calculated by means of magnetic resonance imaging. The planned and achieved positions before and after implantation were compared. RESULTS: The mean light sensitivity ratio between the area actually covered by the chip and that of the planned position was 90.8% with an SD of 11.4%. In two cases with almost perfect positioning, the computed ratio was 100%. Measurements showed that to achieve a 95% sensitivity rate the difference between the planned and achieved chip position must be less than 1.7 mm. Preoperative calculations of the intraocular cable length proved accurate in all cases. CONCLUSIONS: Preoperative evaluation of retinal structures and eye morphology is useful for guiding a retinal implant to the designated area. It is a meaningful tool for planning and performing retinal chip implantation, and it optimizes personalized implantation. (ClinicalTrials.gov numbers, NCT00515814, NCT01024803.).

[Vision restoration with implants in retinal degenerations]. / Látásjavító implantátumok látóhártya-degenerációkban.

Up until now there has been no available treatment for diseases causing the permanent impairment of retinal photoreceptors. Currently the development of the retinal prostheses is the earliest to promise a result that can be implemented in the clinical treatment of these patients. Implants with different operating principles and in various stages of progress are presented in details, highlighting the characteristics, as well as the Hungarian aspects of the development. This survey intends to provide an overview on retinal prostheses, implantable in case of degenerative diseases of the retina, by reviewing and assessing the papers published in relevant journals and based on personal experience. Developments in microelectronics in recent years made it possible and proved to be feasible to replace the degenerated elements in the retina with electrical stimulation. Multiple comparable approaches are running simultaneously. Two types of these implants are directly stimulating the remaining living cells in the retina. Hitherto the finest resolution has been achieved with the subretinal implants. Although the epiretinal implant offer lower resolution, but requires shorter surgery for implantation. Retinal implants in certain retinal diseases are proved to be capable of generating vision-like experiences. A number of types of retinal implants can be expected to appear in clinical practice a few years after the successful conclusion of clinical trials.

P21, p27, bax, cathepsin and survivin pathways in macular dystrophy corneas.

The purpose of our study was to elucidate pathways of genetically programmed cell death (apoptosis) in corneas with macular dystrophy. 10 corneal buttons (10 patients) with macular dystrophy and 8 buttons (8 patients) from enucleated eyes with chorioideal melanoma (controls) were analysed histologically. Immunohistochemical analysis was performed to investigate the presence of p21, p27, bax, cathepsin and survivin proteins. The number of positive cells was determined by analysis of 100 cells and given in percentages. The bax protein was present in 25.6% of epithelial cells in macular dystrophy corneas but was absent in controls. P21 and p27 were found in 35.7 and 87.5% of epithelial cells of macular dystrophy corneas, respectively, but again not in control tissue. In contrast, a lower percentage of cathepsin-positive (30.7% vs 58.8%) and survivin-positive cells (37.6% vs 52.1%) were present in epithelial cells of macular dystrophy corneas than in control epithelial cells. The difference reached statistical significance in the expression of p21 and p27 genes (p<0.05 in both). P21 was positive in 3% of keratocytes, p27 in 1% of endothelial cells of macular dystrophy corneas but negative in controls (0%). Bax, cathepsin and survivin immunopositivity was not detected in keratocytes or endothelial cells of either group. We conclude that the down-regulation of p21, p27 and cathepsin in epithelial cells of macular dystrophy corneas may be related to defense mechanisms against apoptotic cell death.

P53, CD95, cathepsin and survivin pathways in Fuchs' dystrophy and pseudophakic bullous keratopathy corneas.

Our purpose was to elucidate the pathways of apoptosis of corneas with Fuchs' dystrophy and pseudophakic bullous keratopathy. Sixteen corneal buttons (14 patients, median age 73 years) with Fuchs' dystrophy, 13 with pseudophakic bullous keratopathy (PBK) (13 patients, median age 69 years) and 8 buttons (8 patients, median age 59 years) from enucleated eyes with chorioideal melanoma (controls) were analysed histologically. Immunohistochemical analysis was performed to investigate the expression of p21, p27, p63, survivin, CD95, cathepsin, bax, bcl-2 and Ki67. Positive immunohistochemical reactions were detected in epithelial cells of the corneas, but keratocytes and endothelial cells were not positive in any of the groups or stainings. The number of p27 and survivin positive epithelial cells was significantly lower (p=0.048 and 0.041) and the number of cathepsin positive epithelial cells was significantly higher (p=0.004) in Fuchs' dystrophy corneas compared to controls. In pseudophakic bullous keratopathy, p21 and p27 positive epithelial cells were present in a significantly lower (p=0.02 and 0.005) number than in controls. We conclude that genetically programmed cell death is related to the p27, cathepsin and survivin pathways in Fuchs' dystrophy and to the p21 and p27 pathways in pseudophakic bullous keratopathy.

Cell adhesion molecules in stromal corneal dystrophies.

The aim of the present study was to investigate the expression pattern of different cell adhesion molecules in corneal stromal dystrophies. Fifteen corneal buttons from patients diagnosed with three different types of stromal corneal dystrophies and healthy corneas were investigated. Paraffin embedded sections were stained immunohistochemically with monoclonal antibodies against human intercellular adhesion molecule-1 (ICAM-1), endothelial selectin (E-selectin) and endothelial cadherin (E-cadherin) using the avidin-biotin-peroxidase-complex technique. The sections were compared to normal eye bank controls. In corneas from granular dystrophy patients ICAM-1 was expressed focally in epithelial cells and in keratocytes, and expressed diffusely in endothelial cells. In corneas from macular dystrophy patients diffuse epithelial staining was observed and the stromal and endothelial expression was found to be similar to that of granular dystrophy. In lattice dystrophy, only the epithelial cells and endothelium were intensively positive for ICAM-1. E-selectin was not present on any layer of the corneal specimens. E-cadherin was observed only in the epithelium of all three types of corneal dystrophies. Normal corneas did not express any of the investigated adhesion molecules. We found different expression patterns of adhesion molecules in corneas from stromal dystrophies. Our results suggest that adhesion molecules may be involved in the pathogenesis of corneal stromal dystrophies.

The role of lumican and keratocan genes in persistent subepithelial corneal haze following excimer laser photorefractive keratectomy.

PURPOSE: A retrospective clinical and a genetic study was carried out of severe subepithelial corneal haze occurring after photorefractive keratectomy (PRK). Since this clinical condition resembles the lumican-null mouse phenotype, mutation analysis of lumican and keratocan was carried out to investigate whether germline genetic alterations have an effect on development of severe corneal haze in humans. Corneal thickness, photoablation depth, and severity of persistent corneal haze were also analyzed. In vivo confocal microscopy examination was also performed to study corneal structure and endothelial cells. METHODS: Severity of corneal haze was evaluated by slit-lamp biomicroscopy according to Hanna's scale. Corneal structure and endothelial cell shapes and density were viewed with a scanning confocal microscope. PCR-based mutational analysis was performed using temperature gradient gel electrophoresis (TGGE) and direct sequencing. RESULTS: Preoperative corneal thickness was normal (539+/-23.13 microm, mean+/-SD), and the photoablation depth was 88.94+/-18.64 microm (mean+/-SD). The most severe corneal haze was grade 2.0 on Hanna's scale one year after PRK. In vivo confocal microscopy also showed normal endothelial cell density and morphology. Aside from an intronic polymorphism in a control, no genetic alterations were found in the lumican and keratocan genes. CONCLUSIONS: There was no evidence that endothelial dysfunction and germline mutation of lumican and keratocan genes participate in the etiology of subepithelial corneal haze. Our findings suggest that the mechanisms of the development of severe corneal opacity are different in humans after PRK compared to the lumican deficient knockout mouse model.

[Photodynamic therapy in age-related macular degeneration]. / Fotodinámiás kezelés idoskori maculadegenerációban.

INTRODUCTION: Exudative form of age-related macular degeneration is the leading cause of legal blindness in elderly. PURPOSE: The purpose of this study is to report 3.5 years experience with photodynamic therapy in this disorder. PATIENTS AND METHODS: Patient files of all patients underwent photodynamic therapy with verteporfin in Department of Ophthalmology, Semmelweis University, Budapest in a 3.5 years period were reviewed. Changes in visual acuity were considered as main outcome variable compared to natural history data. RESULTS: From April, 2000 to September 2003, 302 patients were treated using photodynamic therapy with verteporfin for exudative form of age-related macular degeneration. The mean change of visual acuity were 2.6 and 2,7 lines at 12 and 24 months, respectively, while according to the natural history data 4.2 and 4.5 could have been expected. After 2 years, 83% of the patients had visual acuity better than or equal to 20/200 (this is the level of legal blindness), while only 33% was expected according to natural history data. Visual acuity of 20/80 or better (practical ambulatory vision) was found in 39% of the treated eyes (12% in natural history data). There was no severe adverse event. CONCLUSIONS: Photodynamic therapy was found to reduce the risk of severe visual loss. The authors' results confirm the data from the international trials. To achieve good results, good patient compliance and continuous access to the treatment are indispensible.

Spatial distribution of keratan sulfate in the rabbit cornea following photorefractive keratectomy.

PURPOSE: To examine the keratan sulfate content of the stroma and to assess its correlation with the healing process (epithelialization and keratocyte density) after photorefractive keratectomy (PRK). METHODS: Using an Aesculap Meditec MEL 70(G-scan) excimer laser, -6.0 diopters (6.0-mm diameter, 82 microm photoablation depth), PRK was carried out on the right eye of 32 New Zealand pigmented rabbits. After enucleation (at days 1, 4, 7, 14, and 28 and months 2, 3, and 7; sub-groups of 4 animals), fluorescent immunohistochemistry was performed on sections from the central comea using monoclonal mouse anti-keratan-sulfate antibody, immunohistochemistry with proliferative cell nuclear antigen antibody, and hematoxylin-eosin histology. The left, untreated eyes served as controls. Cellular morphology and spatial distribution of keratan sulfate were recorded, stromal thickness measured, and keratocyte density calculated. RESULTS: Keratan sulfate was found on the surface of migrating epithelial cells in the early stage (from days 1 to 7). In the stroma, three phases were noted. (Phase 1) Day 1 to 14, intense granular fluorescence appeared in the anterior stroma with hypocellularity. (Phase 2) Month 1 to 2, newly synthesized lamellar keratan sulfate restored the repopulating anterior stroma. Endothelial cells became keratan sulfate positive, while in the posterior stroma, lamellar-form keratan sulfate increased from week 1 and peaked at month 1 (100% increase). (Phase 3) Month 2 to 7, remodeling and deposition of keratan sulfate was noted, which was produced in phase 2. CONCLUSIONS: Keratan sulfate was found in the epithelium, stroma, and endothelium. By controlling the interlamellar spacing, keratan sulfate plays a role in postoperative edema, remodeling of the corneal stroma, and simultaneous regulation of inflammation after PRK.

Proliferation and apoptosis in the corneal stroma in longterm follow-up after photorefractive keratectomy.

This study aimed at investigating the proliferation and apoptosis of corneal cells following photorefractive keratectomy (PRK) treatment. PRK (-6.0 D correction) was performed with the Asclepion-Meditec MEL70 G-scan excimer laser on the right eye of each of 33 rabbits under combined local and general anaesthesia. Animals were sacrificed at 4 h, 1, 4, 7, 14, 28, 56, and 112 days postoperatively, and corneal samples from these eight groups were examined histologically. Stromal cell proliferation was evaluated by immunocytochemical analysis of Ki67. Apoptosis was detected using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay method. The untreated left eyes served as controls. Ki67 positivity was detected in the upper stroma on day 1, 4, 7, and 14, and keratocyte apoptosis on day 1, 4, 7, and 14 after PRK, but not at an earlier or later time. Neither Ki67 positivity nor apoptotic activity was observed in the controls (untreated corneas). PRK was found to trigger proliferation and apoptosis of corneal keratocytes. The frequency and spatial distribution of keratocyte proliferation and apoptosis are likely to be important determinants of the corneal wound healing process, but the detailed regulatory mechanisms have not yet been characterized.

[Intraocular tumours]. / Intraocularis daganatok.

Intraocular tumours may be benign or malignant. The latter are more numerous, and endanger not only vision but life as well. Two of them deserve special attention: melanoma malignum oculi in adults and retinoblastoma in children. Melanoma malignum may arise from all three areas of the uvea: the iris, the ciliary body and the choroid. The more malignant growths are those which are situated closer to the posterior pole. Histologically the epitheloid cell-type of melanoma is more malignant than those containing only spindle cells. Their treatment depends on the size: in the case of large tumours enucleation is required, while for the smaller ones, radiation therapy can be applied. Retinoblastoma is most common in children of 1-2 years of age. It has familial and sporadic forms. Sixty-seven percent of the inherited-type cases are bilateral. An early symptom in small children is strabismus. A white tissue mass growing into the vitreous is seen on the fundus. A diagnostic feature that can be detected by ultrasound examination is calcification. The tumour may also present intracranially, therefore CT of the skull should be performed in each case. Histologically the tumour contains malignant neuroepithelial cells, which may form a rosette. In the case of large tumours the treatment is enucleation; in bilateral processes the bulbus with the larger mass is removed and the other eye is treated with radiation therapy. In both cases chemotherapy is used according to a prescribed schedule. Metastases to the eye occur most frequently from carcinomas of the breast, lungs or gastrointestinal tract. These are treated with radiotherapy, chemotherapy and hormone therapy. Primary intraocular lymphoma often occurs bilaterally, and may be accompanied by primary lymphoma of the central nervous system (CNS). Some benign tumours are found by chance on routine eye examinations, others due to subjective and objective symptoms.

[Results of photorefractive keratectomy in myopia with flying spot excimer laser with high speed and small beam diameter]. / A kis sugárátméroju, nagyfrekvenciás repülopont-technikás excimer lézerkezelés eredményei myopiás szemekben.

PURPOSE: To examine the result of photorefractive keratectomy (PRK) with the next generation of flying spot excimer laser for the treatment of myopic refractive errors. PATIENTS AND METHODS: During the study 164 eyes of 98 patients were assessed. The average age was 29.4 +/- 4.62 years. The myopic eyes were divided into 3 groups: in Group 1. (n = 115 eyes) the eyes between -1.0 D and -6.0 D were evaluated, in this group the preoperative average refraction was -3.43 +/- 1.2 D (SE = spherical equivalent); in Group 2. (n = 31 eyes) the eyes between -6.1 D and -9.0 D were evaluated; the preoperative average refraction was -7.26 +/- 2.4 D (SE). In Group 3. (n = 18 eyes) eyes above -9.0 D were examined; in Group 3. the average preoperative refraction was -10.22 +/- 3.4 D (SE) Follow-up is 6 months. PRK treatments were carried out with the Zeiss Meditec MEL 80 G-Scan flying spot excimer laser, which was operated with a 0.7 mm beam diameter and 250 Hz frequency. RESULTS: In Group 1. The preoperative correction decreased to -0.14 D (SE); in 71% of the treated eyes uncorrected visual acuity (UCVA) was 1.0; in 24% of the eyes UCVA improved to 1.2. Best corrected visual acuity (BCVA) was unchanged in 65% of the eyes; while in 34 improved (in 24% it improved by more than 2) Snellen lines. In Group 2. the preoperative correction decreased to -0.13 +/- 0.01 D (SE); 67% had 1.0 and 8% had a 1.2 UCVA. BCVA was unchanged in 92% in Group 2.; in 8% BCVA increased by 1 or 2 Snellen lines. In Group 3., the preoperative correction decreased to -0.44 +/- 0.2 D (SE); 96% of the eyes had a 0.8 UCVA; BCVA did not change in 75% of the eyes, 25% of the eyes gained 1 Snellen line. CONCLUSIONS: Myopic PRK treatments with the 3rd generation of excimer laser were effective and safe. Regarding BCVA, best results were obtained in the low and medium myopia groups.