Incidence and Mortality of Uveal Melanoma in Hungary: A Nationwide Study.

Uveal melanoma (UM) is the most common primary malignant ocular tumour in adults, although its epidemiology in Central and Eastern Europe is unclear. This study aimed to analyse the incidence and all-cause mortality of UM in Hungary. This nationwide, retrospective, longitudinal study used data from the National Health Insurance Fund and included patients aged ≥18 years who were newly diagnosed with UM (ICD-10 C69.3 or C69.4) between 1 January 2012 and 31 December 2021. Age-standardised incidence and all-cause mortality rates were calculated using European Standard Population data from 2013. We identified 88 and 70 new patients with UM in 2012 and 2021, respectively, showing an almost stable trend. Age-standardised incidence rates varied between 6.40 and 10.96/1,000,000 person-years (PYs) during the analysed period. The highest age-standardised incidence was detected among men (13.38/1,000,000 PYs) in 2015. All-cause mortality decreased from 4.72/1,000,000 PYs to 0.79/1,000,000 PYs between 2012 and 2021. In conclusion, the UM incidence rate in Hungary is comparable to European incidence rates. The incidence did not markedly change, whereas all-cause mortality decreased during the study period, but this decline could not be attributed to improved treatment modalities for primary tumours and metastatic UM.

Clinical Characteristics and Treatment of Ophthalmic Sequelae of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at a Tertiary Eyecare Centre in Hungary.

INTRODUCTION: This study analysed the causative factors and clinical characteristics of acute and chronic ocular sequelae of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) treated at a large third-referral centre in a developed country (Hungary) over a 15-year period. METHODS: This was a retrospective review of patients with acute and/or chronic SJS/TEN who were managed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University in Budapest, Hungary. For each subject, clinical data, including patient demographics, clinical history, causative agents of SJS/TEN, and conservative and surgical treatment details, were reviewed. RESULTS: Ninety-six eyes of 48 patients were included (28 female; 58.3%); the age at disease onset was 32.1 ± 22.4 years. The most common causative factors were medicines (n = 36; 75.0%). Among these drugs, 29.2% were nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 14), 20.8% were antibiotics (n = 10) and 14.6% were antiepileptic drugs (n = 7). In patients with chronic SJS/TEN, the most commonly found ocular sequelae were conjunctival hyperaemia in 45 (56.3%) eyes, symblepharon in 38 (47.5%) eyes, trichiasis/distichiasis in 37 (46.3%) eyes, corneal neovascularization in 31 (38.8%) eyes and corneal scarring in 29 (36.3%) eyes. In patients with chronic SJS/TEN, the most frequently used topical conservative treatment included antibiotics in 53 (66.3%) eyes, preservative-free artificial tears in 50 (62.5%) eyes and topical corticosteroids in 42 (52.5%) eyes of 40 patients. The most frequently performed ocular surgeries for managing chronic ocular sequelae in patients with SJS/TEN were epilation for trichiasis (n = 27; 33.8%), cataract surgery (n = 14; 17.5%), entropion surgery (n = 12; 15.0%), penetrating keratoplasty (PK) (n = 11; 13.8%) and amniotic membrane transplantation (n = 4; 5.0%). CONCLUSION: Our results suggest that NSAIDs, antibiotics and antiepileptic drugs are the most common causative factors for SJS/TEN in Hungary. Like in other countries, in Hungary, the ocular management of patients with acute and chronic SJS/TEN is heterogeneous, and most cases do not follow modern therapeutic guidelines.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

Evaluation of Retinal Blood Flow in Patients with Monoclonal Gammopathy Using OCT Angiography.

BACKGROUND: Monoclonal gammopathy (MG) is characterized by monoclonal protein overproduction, potentially leading to the development of hyperviscosity syndrome. OBJECTIVE: To assess retinal circulation using optical coherence tomography angiography (OCTA) parameters in patients with monoclonal gammopathy. METHODS: OCTA measurements were performed using the Optovue AngioVue system by examining 44 eyes of 27 patients with MG and 62 eyes of 36 control subjects. Superficial and deep retinal capillary vessel density (VD SVP and DVP) in the whole 3 × 3 mm macular and parafoveal area, foveal avascular zone (FAZ) area, and central retinal thickness (CRT) were measured using the AngioAnalytics software. The OCTA parameters were evaluated in both groups using a multivariate regression model, after controlling for the effect of imaging quality (SQ). RESULTS: There was no significant difference in age between the subjects with monoclonal gammopathy and the controls (63.59 ± 9.33 vs. 58.01 ± 11.46 years; p > 0.05). Taking into account the effect of image quality, the VD SVP was significantly lower in the MG group compared to the control group (44.54 ± 3.22% vs. 46.62 ± 2.84%; p < 0.05). No significant differences were found between the two groups regarding the other OCTA parameters (p > 0.05). CONCLUSIONS: A decreased superficial retinal capillary vessel density measured using OCTA in patients with MG suggests a slow blood flow, reduced capillary circulation, and consequent tissue hypoperfusion. An evaluation of retinal circulation using OCTA in cases of monoclonal gammopathy may be a sensitive method for the non-invasive detection and follow-up of early microcirculatory dysfunction caused by increased viscosity.

Micropulse Transscleral Cyclophotocoagulation Results in Secondary Glaucoma.

The aim of this study was to analyze the long-term outcome of first session of micropulse transscleral cyclophotocoagulation (MP-CPC) for refractory glaucoma developed after vitreoretinal surgery combined with silicone oil implantation. The inclusion criteria of this consecutive case series were: patients with secondary glaucoma in the refractory stage who underwent MP-CPC between 2018 and 2021, vitreoretinal surgery combined with silicon oil implantation, and at least a 24-month follow-up period after MP-CPC. Success was defined as the baseline eye pressure reduced at least 20%, and it should be ranged between 10 to 20 mmHg without further MP-CPC at the end of the follow-up. For this retrospective study, 11 eyes of 11 patients were selected. The reduction in IOP was found to be significant (p = 0.004) at the end of the follow-up time, and the success rate was 72% according to our results. The change in the number of antiglaucoma agents in the administered eyedrops was not significant compared to the baseline values. At the end of the follow-up period the change in BCVA values was not significant (p = 0.655). Our results confirm significant IOP lowering effect of this subthreshold method preserving visual performance safely even in eyes with previous vitrectomy surgery with a silicone oil implantation.

Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window.

Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-ß-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations. According to an experimental design, 11 formulations were tested in vitro including two reference formulations by measuring their viscosity, mucoadhesion, drug release and corneal permeability. Finally, two formulations were found promising and investigated further on porcine eyes ex vivo and corneal distribution of nepafenac was determined by RAMAN mapping. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose were ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.

Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD. METHODS: Two clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included. RESULTS: Mean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity. CONCLUSION: Long-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy. TRIAL REGISTRATIONS: VIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

[Ophthalmological results in the Hungarian comprehensive health care screening program, 2011-2022]. / Szemészeti eredmények Magyarország átfogó egészségvédelmi szuroprogramjában, 2011­2022.

INTRODUCTION: The World Health Organisation's VISION 2020 and World report on vision programs prioritize blindness prevention and vision rehabilitation development. The ophthalmology program, which is part of Hungary's comprehensive health care screening program, plays an important role in the national implementation of these. OBJECTIVE: Summary of the results of Hungary's comprehensive health care screening program's ophthalmology program, which has been going on for 12 years. METHOD: The ophthalmological data of 168 522 people aged between 12 and 99 years who participated in the national screening program were analyzed in nine categories: the presence of eye disease, the use of glasses, the refractive power of the glasses, refractive errors (myopia, anisometropia), the functional vision questionnaire, dry eye, colour vision, educational and communication activities. RESULTS: 18.1% of the participants reported having an eye disease, which was much more common in women and the elderly. The proportion of people who wore glasses reached 66%, with roughly one-third of them lacking appropriate glass strength. Myopia was the most common (58.7%) in people aged 18 to 35. Anisometropia was found in 6.5% of people. Women were more likely than men to have dry eyes (26.1%). Men had a higher rate of colour vision deficiency (5.7%) than women (0.7%). DISCUSSION: As blindness is 80% preventable, national screening tests and comprehensive educational activities that contribute to the early detection and treatment of eye diseases are important. It is critical to call attention to the significant growth in the prevalence of myopia in young people as well as the urgent need for the effective implementation of preventive measures. The importance of proper glasses must also be brought to the attention of the general population because incorrect glasses cause visual problems. CONCLUSION: The national ophthalmology screening and educational activity should be continued in the future, with the goal of reducing the incidence of eye diseases associated with visual impairment and increasing the proportion of people who wear appropriate glasses. To stop the spread of myopia, a national preventive and treatment program should be launched. Orv Hetil. 2023; 164(7): 253-259.

Microbiota mitochondria disorders as hubs for early age-related macular degeneration.

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota-mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch's membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)-now called postbiotics-in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

Ocular paraneoplastic pemphigoid / Szemészeti érintettséggel járó paraneoplasiás pemphigoid

Paraneoplastic mucous membrane pemphigoid, a rare pemphigoid variant is associated with primary malignancy, and characterised by fulminant progression and frequent ineffectivity of classical systemic immunosuppression. In this paper, the clinical features, diagnostic and therapeutical challenges are presented through three cases. Detailed history and analysis of the immunofluorescent samples help the diagnosis. The therapeutic goal is to prevent the progression with systemic immunosuppressive treatment, which can be contraindicated during the ongoing oncological therapy. In absence of consent in the exact diagnostic criteria and management protocol of this rare condition, consultation with other specialists (ophthalmologist, dermatologist, dentist, ear-nose-throat specialist, immunologist) has high importance in early diagnosis and treatment.

Ocular treatment of cystinosis with eye drop containing cysteamine / Ciszteamintartalmú szemcsepp alkalmazása cystinosisban

Cystinosis is a rare lysosomal storage disease affecting amino acid metabolism, characterized by the accumulation and crystallization of cystine in various tissues, primarily in the eye and kidney. The major ophthalmic symptom is photophobia, which is related to the corneal deposition of cystine crystals. The light sensitivity significantly impairs the quality of life of the affected patients, thus, effective ophthalmic treatment to reduce the crystal density is very importance. In the current case report, we present the characteristic ocular clinical appearance and treatment options of cystinosis by reviewing the literature. A simple aqueous solution of cysteamine, which aids in the dissolution of crystals, has been widely used in topical treatment in the past, however, its therapeutic efficacy is debatable. Recently, a new viscous formulation of cysteamine has been proposed for ophthalmic treatment. For the treatment of corneal cystine crystals in our patient, the new viscous format of cysteamine has been applied, and therapeutic effects were recorded for a year. Applying the viscous cysteamine formulation, a marked and gradual decrease in photophobia was observed in our patient in the first year of the treatment. Anterior-segment optical coherence tomography and in vivo confocal microscopy represented a continuous decrease in the density of corneal crystals even from the first month of the treatment period. The aim of our case report is to present the ophthalmic symptoms of cystinosis and the results of the first clinical application of viscous formulation of cysteamin eye drops in Hungary in a cystinosis patient.

Intraoperative complication rates in cataract surgery performed by resident trainees and staff surgeons in a tertiary eyecare center in Hungary.

AIM: To compare the incidence of intraoperative complications during primary phacoemulsification (phaco) surgery between resident surgeons (residents) and staff surgeons (specialists) and to objectively determine the difficulty of stages in phaco surgery. METHODS: This retrospective study included cases of phaco cataract surgery performed between January and December 2019. There were no exclusion criteria. For each patient, demographics, clinical history, case complexity, type of surgeon, and operative details were reviewed. Primary outcomes included intraoperative complication rates and the objective measure of difficulty in the steps of the surgery performed by residents and specialists. RESULTS: A total of 3272 cases were included; 7.4% (n=241) of cases were performed by residents. The overall complication rate was 5.4% (n=177). The intraoperative complication rate was significantly higher (P<0.001) in residents (n=33, 13.7%) than in specialists (n=144, 4.8%). The most frequent complications were posterior capsule tear (n=85, 2.6%), anterior capsule tear (n=50, 1.53%), zonular fiber loss (n=45, 1.38%), and dropped nucleus (n=15, 0.46%). Objectively, the most difficult steps during surgery were phaco in 66 (60.0%), capsulorhexis in 21 (19.1%), irrigation/aspiration in 13 (11.8%), hydrodissection in 9 (8.2%), and intraocular lens (IOL) implantation in 1 (0.9%) case. CONCLUSION: Intraoperative complication rates are higher in residents than in specialists. The order of objective difficulty in phaco surgery steps is in line with the subjective findings of other surveys, revealing that the most challenging parts of phaco surgery are phaco and capsulorhexis.

Herpes simplex virus PCR in 2230 explanted corneal buttons.

PURPOSE: To determine herpes simplex virus (HSV) DNA prevalence and mean cycle threshold of polymerase chain reaction (PCR) in corneal tissue of patients with penetrating keratoplasty (PKP), with (HSK+) and without (HSK-) previous clinical herpetic keratitis history. METHODS: Retrospective review of recipient corneal buttons which were explanted through PKP between March 2010 and September 2018 at the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar, Germany. Corneal tissue samples were analysed by real-time PCR for the presence of HSV DNA. For each subject, clinical data, including patients' demographics and clinical diagnoses, were collected. RESULTS: In total, 2230 corneal samples (age at the time of the surgery 57.3 ± 19.2 years) of 1860 patients were analysed. HSV PCR was positive in 137 (6.1%) corneal samples, with a 30.57 ± 6.01 (range 14-39) mean cycle threshold (Ct) value. Two hundred ninety-eight (13.4%) corneas of 266 patients were clinically HSK+, and 1932 (86.6%) corneas of 1600 patients were clinically HSK-. HSV DNA was detected significantly more frequently (p < 0.0001) in HSK+ corneal samples (108 corneal samples; 36.2%), than in HSK- corneal samples (29 corneal samples; 1.5%). Ct value was significantly lower in HSK+ than in HSK- corneal samples (29.8 ± 5.8 versus 32.6 ± 5.9; p = 0.008). CONCLUSION: Our data demonstrate that a positive clinical history of HSK is related to HSV PCR positivity in about every 2.8th patient. In addition, about every 66th explanted corneal tissue is HSV PCR-positive despite the lack of clinical suspicion. These patients may need additional local/systemic antiviral treatment to avoid newly acquired HSK following penetrating keratoplasty.

The effect of systemic factors on retinal blood flow in patients with carotid stenosis: an optical coherence tomography angiography study.

Carotid artery stenosis (CAS) is among the leading causes of mortality and permanent disabilities in the Western world. CAS is a consequence of systemic atherosclerotic disease affecting the majority of the aging population. Optical coherence tomography angiography (OCTA) is a novel imaging technique for visualizing retinal blood flow. It is a noninvasive, fast method for qualitative and quantitative assessment of the microcirculation. Cerebral and retinal circulation share similar anatomy, physiology, and embryology; thus, retinal microvasculature provides a unique opportunity to study the pathogenesis of cerebral small vessel disease in vivo. In this study, we aimed to analyze the effect of systemic risk factors on retinal blood flow in the eyes of patients with significant carotid artery stenosis using OCT angiography. A total of 112 eyes of 56 patients with significant carotid stenosis were included in the study. We found that several systemic factors, such as decreased estimated glomerular filtration rate (eGFR), hypertension, and carotid occlusion have a significant negative effect on retinal blood flow, while statin use and carotid surgery substantially improve ocular microcirculation. Neither diabetes, clopidogrel or acetylsalicylic acid use, BMI, serum lipid level, nor thrombocyte count showed a significant effect on ocular blood flow. Our results demonstrate that a systematic connection does exist between certain systemic risk factors and retinal blood flow in this patient population. OCTA could help in the assessment of cerebral circulation of patients with CAS due to its ability to detect subtle changes in retinal microcirculation that is considered to represent changes in intracranial blood flow.

Association of acute retinal necrosis with ischemic stroke / Akut retinanekrózis és ischaemiás stroke társulása.

Összefoglaló. A varicella zoster vírus (VZV-) fertozés típusos elso megjelenése a bárányhimlo, késobb a reaktiváció során a herpes zoster. Szemészeti tünet az V/I-es agyideget érinto zoster esetén gyakori. A legrettegettebb szemészeti manifesztáció az akut retinanekrózis, mely fulmináns lefolyású, és súlyos szöveti destrukciót, valamint jelentos funkcionális károsodást, gyakran vakságot hagy maga után. Központi idegrendszeri vascularis érintettség elofordulhat bárányhimlohöz társulóan vagy a késobbi reaktivációk során is, súlyos következményekhez vezetve. A Semmelweis Egyetem Szemészeti Klinikáján akut retinanekrózis tünetével érkezo 65 éves férfi esetét ismertetjük. Az Amerikai Szemorvostársaság (AAO) diagnosztikus kritériumainak mindenben megfelelo klinikai kép alapján azonnal indított adekvát dózisú antivirális kezelés mellett 3 nap múlva, contralateralis hemiparesis hátterében, a képalkotó vizsgálat ipsilateralis ischaemiás stroke-ot igazolt. Intraocularis mintából PCR-vizsgálat bizonyította a vírus jelenlétét. Liquormintában enyhe anti-VZV-IgA-pozitivitás mutatkozott. Az aktuális szemészeti betegség és a stroke társulásának hátterében az észlelt paraméterek, valamint a releváns irodalmi adatok alapján a varicella zoster vírus okozta vasculopathiát valószínusítettük. Gyermekkorban ez az ischaemiás stroke leggyakoribb oka, felnottkorban pedig az V/I-es agyideg herpeses érintettsége esetén négy és félszeres a kockázat stroke kialakulására. A VZV-reaktiváció okozta akut retinanekrózis és a stroke társulásának lehetosége, bár ismert a nemzetközi irodalomban, magyar szakirodalom tudomásunk szerint eddig nem tárgyalta, ez kiemeli esetünk közlésének jelentoségét. Orv Hetil. 2021; 162(48): 1940-1945. Summary. The typical first onset of varicella zoster virus (VZV) infection is chickenpox, later herpes zoster during reactivation. Ophthalmic symptoms are common in herpes zoster affecting the V/I cranial nerve. The most dreaded ophthalmic manifestation is acute retinal necrosis, which has a fulminant course and leaves severe tissue damage as well as significant functional impairment, often blindness. Vascular involvement in the central nervous system may occur in association with chickenpox or during subsequent reactivations leading to severe consequences. We report the case of a 65-year-old male patient with symptoms of acute retinal necrosis at the Department of Ophthalmology, Semmelweis University. The clinical picture fulfilled the diagnostic criteria of the American Academy of Ophthalmology (AAO) and after 3 days of the immediately initiated adequate therapy, contralateral hemiparesis appeared, that was confirmed as an ipsilateral stroke by imaging study. The PCR analysis of an intraocular sample confirmed the presence of VZV. Mild anti-VZV IgA positivity was observed in the cerebrospinal fluid sample. Based on the current ophthalmic disease, the associated stroke alongside with the relevant literature data, varicella zoster vasculopathy was probable. VZV vasculopathy is the most common cause of ischemic stroke in childhood and in adulthood herpetic involvement of the V/I cranial nerve elevates 4.5 times the risk of stroke formation. Though the possible association of acute retinal necrosis and stroke caused by VZV reactivation is known in the international literature, to the best of our knowledge it has not been discussed in Hungary so far, which highlights the importance of reporting our case. Orv Hetil. 2021; 162(48): 1940-1945.

Ocular signs and comorbidities in monoclonal gammopathy: Analysis of 84 eyes of 42 subjects / A monoklonális gammopathia szemészeti jelei és szövodményei: 42 beteg 84 szemének vizsgálata

Összefoglaló. Célkituzés: A monoklonális gammopathia szemészeti jeleinek és szövodményeinek vizsgálata. Betegek és módszerek: Két nagy budapesti hematológiai ellátóhely 1999 és 2020 között diagnosztizált és/vagy kezelt, monoklonális gammopathiát mutató betegeit vizsgáltuk (42 beteg 84 szeme, 42,86% férfi; átlagéletkor 63,83 ± 10,76 év). A hematológiai diagnózis 3 esetben bizonytalan jelentoségu monoklonális gammopathia, 34 esetben myeloma multiplex, 3 esetben parázsló myeloma, 1-1 esetben Waldenström-macroglobulinaemia és amyloidosis voltak. Kontrollcsoportként véletlenszeruen kiválasztott, hasonló korcsoportú, hematológiai betegség nélküli egyéneket vizsgáltunk (43 beteg 86 szeme, 32,56% férfi; átlagéletkor 62,44 ± 11,89 év). A szemészeti vizsgálat elott minden személy kitöltötte a Szemfelszíni Betegség Index (OSDI-) kérdoívet. A szemészeti vizsgálat során a látóélesség vizsgálata mellett pupillatágítást követoen réslámpás vizsgálatot végeztünk. Eredmények: Monoklonális gammopathiában az OSDI-érték szignifikánsan magasabb volt, mint a kontrollokban (p = 0,002). Gammopathiában 3 beteg 5 szeménél (5,95%) találtunk potenciális szaruhártya-immunglobulinlerakódást. Gammopathiában szárazszem-betegség 66,67%-ban, szürke hályog 55,95%-ban, Meibom-mirigy-diszfunkció 20,24%-ban, hátsó kérgi szürke hályog 19,05%-ban, egyéb szaruhártyahegek és -homályok 17,86%-ban, krónikus szemhéjgyulladás 14,29%-ban, szemészeti eltérés hiánya 11,90%-ban, macula- és/vagy retinadrusen 9,52%-ban, szaruhártya-immunglobulinlerakódás 5,95%-ban, epiretinalis membrán 5,95%-ban, korábbi szürkehályog-mutét 5,95%-ban, glaucoma 4,76%-ban, Fuchs-dystrophia 2,38%-ban, perifériás retinadegeneráció 2,38%-ban, chorioidea naevus 2,38%-ban, diabeteses retinopathia 1,19%-ban, arteria centralis retinae elzáródás 1,19%-ban, vena centralis retinae ágelzáródás 1,19%-ban, amblyopia 1,19%-ban volt kimutatható. A szárazszem-betegség (p = 0,002), a hátsó kérgi szürke hályog (p = 0,001), a szürke hályog (p<0,00001) és az egyéb szaruhártyahegek és -homályok (p = 0,01) szignifikánsan magasabb arányban fordultak elo a monoklonális gammopathiát mutató betegekben, mint a kontrollokban. Következtetés : Monoklonális gammopathiában a szárazszem-betegség és a szürke hályog a leggyakoribb szemészeti eltérés. A monoklonális gammopathia potenciális szemészeti jelei és szövodményei miatt javasoljuk a betegek évenkénti szemészeti ellenorzését, életminoségük javítása érdekében. Orv Hetil. 2021; 162(38): 1533-1540. OBJECTIVE: To examine ocular signs and ocular comorbidities in monoclonal gammopathy. PATIENTS AND METHODS: We analyzed patients from two large referral hematology centers in Budapest, who were diagnosed and/or treated with monoclonal gammopathy between 1997 and 2020 (84 eyes of 42 patients, 42.86% male, mean age 63.83 ± 10.76 years). Before the ophthalmic examination, the subjects filled in the Ocular Surface Disease Index (OSDI) questionnaire. Ophthalmic examination included visual acuity test and slit-lamp examination following dilation of the pupil. RESULTS: OSDI scores were significantly higher in subjects with monoclonal gammopathy than in controls (p = 0.002). Among gammopathy subjects, we observed potential corneal immunoglobulin deposition in 5 eyes of 3 patients (5.95%). In gammopathy subjects, there was dry eye disease (66.67%), cataract (55.95%), Meibomian gland dysfunction (20.24%), posterior cortical cataract (19.05%), corneal scars and degenerations (17.86%), chronic blepharitis (14.29%), absence of ocular complaint (11.90%), macular or retinal drusen (9.52%), corneal immunoglobulin deposition (5.95%), epiretinal membrane (5.95%), previous cataract surgery (5.95%), glaucoma (4.76%), Fuchs dystrophy (2.38%), peripheral retinal degeneration (2.38%), chorioideal naevus (2.38%), diabetic retinopathy (1.19%), central retinal artery occlusion (1.19%), central retinal vein branch occlusion (1.19%) and amblyopia (1.19%). The proportion of dry eye disease (p = 0.002), posterior cortical cataract (p = 0.001), cataract (p<0.00001), and corneal scars and degenerations (p = 0.01) were significantly higher in gammopathy subjects than in controls. CONCLUSION: Dry eye disease and cataracts are the most common ocular comorbidities in patients with monoclonal gammopathy. Therefore, due to the potential ocular signs and comorbidities of monoclonal gammopathy, we suggest a regular, yearly ophthalmic checkup of these patients to improve their quality of life. Orv Hetil. 2021; 162(38): 1533-1540.

Ophthalmic use of TNFα inhibitor: adalimumab treatment in uveitis / A TNFα-gátló szemészeti alkalmazása: adalimumabkezelés uveitisben.

Összefoglaló. Bevezetés: Az adalimumab egy TNFα-gátló monoklonális antitest; számos indikációja közül a nem fertozéses eredetu intermedier, posterior és panuveitisek kezelésében is általánosan alkalmazható készítmény. Célkituzés: A felnottkori nem fertozéses eredetu uveitis miatt adalimumabkezelést kapó betegekkel szerzett tapasztalataink összefoglalása. Betegek és módszerek: Retrospektív esetsorozatban vizsgáljuk a budapesti Uveitis Centrumban (a Semmelweis Egyetem Szemészeti Klinikájának Uveitis Ambulanciáján) 2018 és 2020 között adalimumabbal kezelt felnott, nem fertozéses eredetu uveitises eseteinket. Eredmények: 13 beteget mutatunk be (8 no, 5 férfi), átlagéletkor 45 (26-80) év. Az adalimumabot 12 beteg Humira, 1 beteg Amgevita készítmény formájában kapja. Az uveitis eredete 2 esetben 'birdshot' chorioretinitis, 2 esetben Behçet-kór, 1 esetben sarcoidosis, 3 esetben retinalis vasculitis, 1 esetben Vogt-Koyanagi-Harada-betegség volt, és 4 esetben idiopathiás eredetunek bizonyult. Az adalimumabkezelést 7 betegnél kellett elhagyni, elsosorban terápiás elégtelenség miatt, míg 6 betegnél jelenleg is eredményesen folyik a kezelés. Következtetés: Tapasztalataink alapján az adalimumab biztonságos, kevés mellékhatással bíró, hatékony kezelés számos uveitisformában önmagában adva vagy kis dózisú szteroiddal kiegészítve. Korábbi terápiákra (szteroid, immunszuppresszió) rezisztens esetekben is alkalmazható. A szemészetben a szisztémás biológiai terápia, az adalimumab bevezetése az uveitises betegek kezelésében a látóélesség megorzése szempontjából sorsdönto jelentoségu. Orv Hetil. 2021; 162(34): 1370-1375. INTRODUCTION: Adalimumab is a monoclonal antibody that inhibits TNFα and among other indications it can be a systemic treatment in the non-infectious intermediate, posterior and panuveitis. OBJECTIVE: To summarize our experience in patients receiving adalimumab for adult non-infectious uveitis. PATIENTS AND METHODS: We investigate our adult cases of non-infectious uveitis treated with adalimumab between 2018 and 2020 in a retrospective case series at the Uveitis Center in Budapest (Semmelweis University, Department of Ophthalmology, Uveitis Department). RESULTS: We present 13 patients (8 females, 5 males) with a mean age of 45 (26-80) years. Adalimumab is given to 12 patients as Humira and 1 patient as Amgevita. The etiology of uveitis was in 2 cases birdshot chorioretinitis, 2 Behçet's disease, 1 sarcoidosis, 3 retinal vasculitis, 1 Vogt-Koyanagi-Harada disease, and 4 of idiopathic origin. Adalimumab treatment had to be discontinued in 7 cases, mainly due to therapeutic insufficiency, while in 6 cases we are still successfully treating patients. CONCLUSION: According to our experience, adalimumab is a safe and effective treatment, with minimal side effect in many forms of uveitis alone, or in combination with a low-dose steroid. It can also be used in cases where traditional immunosuppressive therapies are ineffective. In ophthalmology, systemic biologic therapy, availability of adalimumab in the treatment of uveitis is crucial for maintaining visual acuity at affected patients. Orv Hetil. 2021; 162(34): 1370-1375.

Ocular Signs and Ocular Comorbidities in Monoclonal Gammopathy: Analysis of 80 Subjects.

PURPOSE: To examine the ocular signs of monoclonal gammopathy and to evaluate ocular comorbidities in subjects with monoclonal gammopathy. Patients and Methods. We analyzed patients from two large referral hematology centers in Budapest, diagnosed and/or treated with monoclonal gammopathy between 1997 and 2020. As a control group, randomly selected individuals of the same age group, without hematological disease, have been included. There were 160 eyes of 80 patients (38.75% males; age 67.61 ± 10.48 (range: 38-85) years) with monoclonal gammopathy and 86 eyes of 43 control subjects (32.56% males; age 62.44 ± 11.89 (range 37-86) years). The hematological diagnosis was MGUS in 9 (11.25%), multiple myeloma in 61 (76.25%), smoldering myeloma in 6 (7.50%), and amyloidosis or Waldenström macroglobulinemia in 2 cases (2.50%-2.50%). Before detailed ophthalmic examination with fundoscopy, 42 subjects with gammopathy (52.50%) and all controls filled the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: The OSDI score and best-corrected visual acuity (BCVA) were significantly worse in subjects with monoclonal gammopathy than in controls (p=0.02; p=0.0005). Among gammopathy subjects, we observed potential corneal immunoglobulin deposition in 6 eyes of 4 (3.75%) patients. Ocular surface disease (p=0.0001), posterior cortical cataract (p=0.01), and cataract (p=0.0001) were significantly more common among gammopathy subjects than in controls (χ 2 test). CONCLUSIONS: Ocular surface disease and cataract are more common, and BCVA is worse in patients with monoclonal gammopathy than in age-matched controls. Therefore, and due to the potential ocular signs and comorbidities of monoclonal gammopathy, we suggest a regular, yearly ophthalmic checkup of these patients to improve their quality of life.

Clinical Review of Ocular Traumas Resulting in Enucleation or Evisceration in a Tertiary Eye Care Center in Hungary.

PURPOSE: To analyse the demographic and clinical characteristics of ocular traumas resulting in enucleation/evisceration in a large tertiary referral center in a developed country (Hungary) over a period of 15 years. Patients and Methods. A retrospective review of enucleated/eviscerated eyes that underwent surgery between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University, Budapest, Hungary, due to ocular trauma as the primary indication for enucleation/evisceration. For each subject, clinical history, B-scan ultrasound report, and histopathology results were reviewed. RESULTS: There were 124 enucleated/eviscerated eyes from 124 patients (91 males (73.4%)). The mean age at the time of trauma was 37.3 ± 26.0 years while the mean age at the time of enucleation/evisceration was 46.9 ± 20.3 years. The main clinical diagnoses after ocular trauma were open globe injury (n = 96; 77.4%), ocular burns (n = 6; 4.8%), traumatic optic neuropathy (n = 4; 3.2%), bulbar avulsion (n = 3; 2.4%), traumatic cataract (n = 2; 1.6%), retinal ablation (n = 1; 0.8%), and traumatic carotid-cavernous fistula (n = 1; 0.8%). Among the 124 patients, 98 (79.0%) underwent enucleation and 26 (21.0%) evisceration. Patients who underwent primary enucleation/evisceration (n = 24 19.4%) were significantly older at the time of the injury (57.7 ± 22.7 years) than people who underwent secondary eye removal (32.4 ± 24.4 years) (p < 0.0001). The mean time interval between trauma and enucleation/evisceration was 114.9 ± 163.5 months. The main clinical indications for anophthalmic surgery were atrophia/phthisis bulbi (n = 56, 45.2%), acute trauma (n = 25, 20.2%), painful blind eye due to glaucoma (n = 17, 13.7%), endophthalmitis (n = 10, 8.1%), and cosmetic reasons (n = 7, 5.6%). One patient (0.8%) had sympathetic ophthalmia. CONCLUSIONS: Primary enucleation/evisceration was performed in one-fifth of all ocular trauma-related anophthalmic surgeries in our tertiary eye care center with enucleation being the most common procedure. Atrophia/phthisis bulbi was the most frequent immediate clinical indication for enucleation/evisceration.