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.

[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.

Fixation stability after surgical treatment of strabismus and biofeedback fixation training in amblyopic eyes.

BACKGROUND: Visual fixation may be affected in amblyopic patients and, moreover, its stability may be associated with the effects of amblyopic treatments on visual performance in patients with strabismus. Therefore, fixation stability is a relevant biomarker that might predict the recurrence of amblyopia after a therapeutic intervention. Microperimetric biofeedback fixation training (BFT) can stabilize visual fixation in adult patients with central vision loss. It was the purpose of the present study to evaluate the effects of BFT on fixation stability in adult amblyopic patients after surgical intervention to treat strabismus. METHODS: Participants were 12 patients with strabismus (mean age = 29.6 ± 8.5 years; 6 females) and 12 healthy volunteers (mean age = 23.8 ± 1.5 years; 9 females). The protocol included ophthalmological and microperimetric follow-ups to measure fixation stability and macular sensitivity. BFT was applied monocularly to four amblyopic eyes either on the spontaneous preferential retinal locus or to a fixation area closer to the anatomical fovea after surgical treatment of strabismus. RESULTS: Baseline measurements showed significantly altered microperimetric average threshold in amblyopic eyes compared to fellow eyes (p = 0.024) and compared to control eyes (p < 0.001). Fixation was unstable in amblyopic eyes compared to control eyes (p < 0.001). Fixation stability did not significantly change after surgical alignment of strabismus (p = 0.805). BFT applied to operated eyes resulted in a more stable fixation with improvements of about 50% after three months of training. CONCLUSIONS: Fixation stability improvements following BFT highlight its potential use in adult amblyopic eyes after the surgical alignment of the strabismus. Future investigations may also consider applying this method in combination with standard treatments to improve vision in amblyopic patients.

Recently updated global diabetic retinopathy screening guidelines: commonalities, differences, and future possibilities.

Diabetic retinopathy (DR) is a global health burden. Screening for sight-threatening DR (STDR) is the first cost-effective step to decrease this burden. We analyzed the similarities and variations between the recent country-specific and the International Council of Ophthalmology (ICO) DR guideline to identify gaps and suggest possible solutions for future universal screening. We selected six representative national DR guidelines, one from each World Health Organization region, including Canada (North America), England (Europe), India (South- East Asia), Kenya (Africa), New Zealand (Western Pacific), and American Academy of Ophthalmology Preferred Practice Pattern (used in Latin America and East Mediterranean). We weighed the newer camera and artificial intelligence (AI) technology against the traditional screening methodologies. All guidelines agree that screening for DR and STDR in people with diabetes is currently led by an ophthalmologist; few engage non-ophthalmologists. Significant variations exist in the screening location and referral timelines. Screening with digital fundus photography has largely replaced traditional slit-lamp examination and ophthalmoscopy. The use of mydriatic digital 2-or 4-field fundus photography is the current norm; there is increasing interest in using non-mydriatic fundus cameras. The use of automated DR grading and tele-screening is currently sparse. Country-specific guidelines are necessary to align with national priorities and human resources. International guidelines such as the ICO DR guidelines remain useful in countries where no guidelines exist. Validation studies on AI and tele-screening call for urgent policy decisions to integrate DR screening into universal health coverage to reduce this global public health burden.

Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with International Myopia Institute.

The prevalence of myopia is increasing extensively worldwide. The number of people with myopia in 2020 is predicted to be 2.6 billion globally, which is expected to rise up to 4.9 billion by 2050, unless preventive actions and interventions are taken. The number of individuals with high myopia is also increasing substantially and pathological myopia is predicted to become the most common cause of irreversible vision impairment and blindness worldwide and also in Europe. These prevalence estimates indicate the importance of reducing the burden of myopia by means of myopia control interventions to prevent myopia onset and to slow down myopia progression. Due to the urgency of the situation, the European Society of Ophthalmology decided to publish this update of the current information and guidance on management of myopia. The pathogenesis and genetics of myopia are also summarized and epidemiology, risk factors, preventive and treatment options are discussed in details.

Impact of COVID-19 Pandemic on Emergency Inpatient Volume at a Tertiary Eye Care Center in Germany with Corneal Main Specialization.

BACKGROUND: To estimate the impact of the COVID-19 pandemic on emergency inpatient volume in a tertiary eye care center in Germany with corneal main subspecialization. MATERIAL AND METHODS: A retrospective review of ocular emergency patients who attended the inpatient unit of the Department of Ophthalmology of Saarland University, Homburg/Saar, Germany during the COVID-19 pandemic, between 1 March and 30 April 2020, in comparison to the same time period in 2019. For each subject, clinical history and surgical reports were reviewed. After 24 March 2020, PCR examinations for SARS-CoV-2 were performed from throat swab specimens in all patients using real-time RT-PCR. RESULTS: Totally, 135 patients were admitted in 2019 and 115 patients in 2020 as emergency cases. The patient age at the time of admission did not differ significantly between the two time periods (63.6 ± 17.9 years vs. 62.5 ± 19.6 years) (p = 0.792), but the average length of hospital stays increased significantly for 2020 (4.0 ± 3.6 vs. 4.4 ± 2.7 days, p = 0.043). The percentage of admissions due to acute corneal hydrops (0% vs. 3.5%) increased significantly from 2019 to 2020 (χ2 = 4.772, p = 0.028), however, there was not a significant difference between the two years for any other diagnosis (χ2 ≤ 3.564, p ≥ 0.059). From 2019 to 2020, the percentage of acute intravitreal anti-VEGF injections decreased significantly (7.9% vs. 1.3%, χ2 = 3.985, p = 0.045), but the proportion of other emergency surgeries did not differ between the two years (χ2 ≤ 3.617, p ≥ 0.057). COVID-19 PCR examination was performed in 66 (57.4%) cases in 2020 and all samples (100%) were negative. CONCLUSIONS: The COVID pandemic did not change emergency inpatient volume in our department, but duration of hospital stay was extended on average by 8 hours, mainly due to additional COVID-19-PCR examinations. The proportion of the most frequently performed surgeries did not change remarkably between 2019 and 2020, but with the introduction of Muraine's sutures in 2019, the percentage of admissions with acute corneal hydrops (with or without subsequent surgery) increased for 2020. No urgent surgery had to be postponed due to the COVID-19 pandemic at our department; all operations were performed successfully.

Model-based economic burden of diabetic retinopathy in Hungary / A cukorbetegség szemészeti szövodményeinek modellalapú költségterhe Magyarországon.

Összefoglaló. Bevezetés: A diabeteses retinopathia minden harmadik cukorbeteget érinti a világban, és a dolgozó korú lakosság körében a vakság vezeto oka. Célkituzés: Tanulmányunk célja a diabeteses retinopathia prevalenciaalapú költségterhének meghatározása 2018-ban a 18 évnél idosebb korú lakosság körében Magyarországon. Módszer: Standardizált 'rapid assessment of avoidable blindness' (RAAB) + diabeteses retinopathia modul alapú metodikán alapuló modellel analizáltuk a diabeteses retinopathia költségterhét. A diabeteses retinopathia okozta gazdasági terhet a Nemzeti Egészségbiztosítási Alapkezelo és a páciensek oldaláról felmerülo költségeket analizálva vizsgáltuk. A prevalenciaalapú diabeteses retinopathia költségmodellt a skót diabeteses retinopathia klasszifikációnak és a diabeteses retinopathia súlyossági stádiumának megfeleloen állítottuk össze. Eredmények: A diabeteses retinopathia költségterhe 43,66 milliárd Ft volt 2018-ban. A két fo költségviselo az anti-VEGF-injekciók (28,91 milliárd Ft) és a vitrectomiák (8,09 milliárd Ft) voltak. Ez a két kezelési mód volt felelos a diabeteses retinopathiával kapcsolatban felmerülo összes költség 84,7%-áért. Az egy páciensre jutó átlagos költségteher 54 691 Ft volt hazánkban. Következtetés: A cukorbetegek szemészeti járó- és fekvobeteg-ellátása alulfinanszírozott hazánkban. A proliferatív diabeteses retinopathia és a diabeteses maculaoedema növekvo társadalmi-gazdasági terhe miatt érdemes volna javítani a megelozés, a szurés és a korai kezelés jelenlegi helyzetén. Orv Hetil. 2021; 162(8): 298-305. INTRODUCTION: Diabetic retinopathy affects every third people with diabetes mellitus in the world and is the leading cause of blindness in adults of working age. OBJECTIVE: The aim of this study was to analyse the economic burden associated with diabetic retinopathy in people aged 18 years and older in Hungary. METHOD: Rapid assessment of avoidable blindness (RAAB) with the diabetic retinopathy module (DRM) based diabetic retinopathy cost model study was conducted in Hungary in 2018. Economic burden of diabetic retinopathy was analysed from the perspective of the National Health Insurance Fund system and the patients. Our prevalence-based diabetic retinopathy cost model was performed according to the Scottish diabetic retinopathy grading scale and based on the diabetic retinopathy severity stadium. RESULTS: The total diabetic retinopathy-associated economic burden was 43.66 billion HUF in 2018. The two major cost drivers were anti-VEGF injections (28.91 billion HUF) and vitrectomies (8.09 billion HUF) in Hungary; they covered to 84.7% of the total cost among people with diabetes mellitus. The diabetic retinopathy-related cost per patient was 54 691 HUF in Hungary. CONCLUSION: Outpatient and inpatient eye care of people with diabetes mellitus are underfinanced in Hungary. Due to the increasing socio-economic burden of proliferative diabetic retinopathy and diabetic macular oedema, it would be important to invest in proliferative diabetic retinopathy and macular oedema prevention, screening and early treatment. Orv Hetil. 2021; 162(8): 298-305.

Rapid assessment of avoidable blindness-based healthcare costs of diabetic retinopathy in Hungary and its projection for the year 2045.

BACKGROUND/AIMS: The purpose of this study was to estimate the total healthcare cost associated with diabetic retinopathy (DR) in the population aged 18 years and older in Hungary, and its projection for the year 2045. METHODS: A cost model was developed based on the standardised rapid assessment of avoidable blindness with the diabetic retinopathy module (RAAB+DRM) methodology and recently reported prevalent-based cost of illness model. Projection for 2045 was made based on the estimation for increasing diabetes mellitus (DM) prevalence of the International Diabetes Federation. Costs were analysed from the perspective of the healthcare system and the patients. Our DR cost model was constructed according to the Scottish DR grading scale and based on the DR severity stadium. RESULTS: The total DR-associated healthcare cost was US$145.8 million in 2016 and will increase to US$169.0 million by 2045. The two major cost drivers were intravitreal antivascular endothelial growth factor injections and vitrectomies in this study (US$126.4 million in 2016 and US$146.5 million in 2045); they amounted to 86.7% of the total treatment cost of DR. The DR-related cost per patient was US$180.5 in Hungary. CONCLUSIONS: The cost per patient for treating DR was lower in Hungary than in other countries. Due to the increasing socioeconomic burden of proliferative DR and diabetes-related blindness, it would be important to invest in DR screening, prevention and early treatment. Our new RAAB-based cost of DR model may facilitate comparisons of DR treatment costs across countries.

Relationship between diabetes mellitus and cataract in Hungary.

AIM: To examine the coexistence of diabetes mellitus (DM) and cataract in Hungary. The effects of DM on the cataract surgical results were also in the focus of analysis. METHODS: Statistical data analysis of the results of the Rapid Assessment of Avoidable Blindness with Diabetic Retinopathy (RAAB+DR) module conducted in Hungary in 2015. This cross-sectional, population-based, national survey included 3523 people aged 50 years and over. Participants of the survey were examined on-site. Visual acuity, main cause for visual impairment (using direct and indirect ophthalmoscopes), in case of best corrected visual acuity (BCVA) ≤0.5 and blood glucose level (random test with glucometer) were examined. RESULTS: The prevalence of cataract was 23.4%, and DM was 20.0%. The occurrence of cataract steadily increased with age. Among the examined participants with DM, the prevalence of cataract was significantly (P=0.012) higher (+35%) than that in non-diabetic subjects (29.5% vs 21.8%). Following aging (OR=15.2%, P<0.001), DM proved to be the most independent influencing risk factor (OR=49.9%, P<0.001). The presence of DM was neither an influencing factor for complications of cataract surgery, nor for postoperative visual acuity. CONCLUSION: DM appears to be one of the main risk factors for developing cataract. Other risk factors, such as age, sex and environment also play an influencing role. Diabetes does not seem to affect the occurrence of cataract surgical complications.

Cataract blindness in Hungary.

AIM: To estimate the prevalence of blindness and visual impairment resulting from cataract in the population aged ≥50y in Hungary, and to assess the cataract surgical services. METHODS: A rapid assessment of avoidable blindness (RAAB) was conducted. A total of 3523 eligible people were randomly selected and examined. Each participant underwent surgery for cataract was interviewed with regard to the year, place, and costs of the surgery. Participants with obvious cataract were asked why they had not yet undergone surgery (barriers to surgery). RESULTS: An estimated 12 514 people were bilaterally blind; the visual acuity (VA) in 19 293 people was <6/60, and the VA in 73 962 people was <6/18 in the better eye due to cataract. An estimated 77 933 eyes are blind; 98 067 eyes had a VA of <6/60, and an estimated 277 493 eyes had a VA of <6/18 due to cataract. Almost all cataract surgeries were conducted in government hospitals. The age- and sex-adjusted cataract surgical coverage with VA<3/60 in eyes was 90.0%. The rate of good visual outcome after surgery was 79.5%. Ocular comorbidity was the main cause of poor outcome (78.1%), followed by late complications (such as posterior capsule opacification) (17.2%), inadequate optical correction (3.1%), and surgical complications (1.6%). The main barrier to surgery in people with bilateral cataract and VA of <6/60 was 'need not felt'. CONCLUSION: The prevalence of visual impairment resulting from cataract is slightly higher than expected. The quality of the cataract surgical service seems adequate in Hungary. However, the number of cataract operations per year should continue to increase due to the increasing patient demands and the aging population.

Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans.

Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

Preventing blindness and visual impairment in Europe: What do we have to do?

Severe visual impairment and blindness are significant public health problems worldwide. Four-fifths of cases of blindness can be prevented or cured. The World Health organisation's 'Universal Eye Health: A Global Action Plan 2014-2019' and the European Society of Ophthalmology's Pilot Committee on Public Eye Health are aiming to decrease the prevalence of blindness in Europe and around the world. Starting discussions addressing possible actions and advocacies to improve current circumstances in public eye health is a common task of ophthalmologists and public health specialists in Europe.

Active forms of Akt and ERK are dominant in the cerebral cortex of newborn pigs that are unaffected by asphyxia.

AIMS: Perinatal asphyxia (PA) often results in hypoxic-ischemic encephalopathy (HIE) in term neonates. Introduction of therapeutic hypothermia improved HIE outcome, but further neuroprotective therapies are still warranted. The present study sought to determine the feasibility of the activation of the cytoprotective PI-3-K/Akt and the MAPK/ERK signaling pathways in the subacute phase of HIE development in a translational newborn pig PA/HIE model. MAIN METHODS: Phosphorylated and total levels of Akt and ERK were determined by Western blotting in brain samples obtained from untreated naive, time control, and PA/HIE animals at 24-48h survival (n=3-3-6,respectively). PA (20min) was induced in anesthetized piglets by ventilation with a hypoxic/hypercapnic (6%O220%CO2) gas mixture. Furthermore, we studied the effect of topically administered specific Akt1/2 and MAPK/ERK kinase inhibitors on Akt and ERK phosphorylation (n=4-4) in the cerebral cortex under normoxic conditions. KEY FINDINGS: PA resulted in significant neuronal injury shown by neuropathology assessment of haematoxylin/eosin stained sections. However, there were no significant differences among the groups in the high phosphorylation levels of both ERK and Akt in the cerebral cortex, hippocampus and subcortical structures. However, the Akt1/2 and MAPK/ERK kinase inhibitors significantly reduced cerebrocortical Akt and ERK phosphorylation within 30min. SIGNIFICANCE: The major finding of the present study is that the PI-3-K/Akt and the MAPK/ERK signaling pathways appear to be constitutively active in the piglet brain, and this activation remains unaltered during HIE development. Thus, neuroprotective strategies aiming to activate these pathways to limit apoptotic neuronal death may offer limited efficacy in this translational model.

Subjective health expectations of patients with age-related macular degeneration treated with antiVEGF drugs.

BACKGROUND: Subjective expectations regarding future health may influence patients' judgement of current health and treatment effects, as well as adherence to therapies in chronic diseases. We aimed to explore subjective expectations on longevity and future health-related quality of life (HRQOL) of patients with age-related macular degeneration (AMD) treated with antiVEGF injections and analyse the influencing factors. METHODS: Consecutive AMD patients in two ophthalmology centres were included. Demographics, clinical characteristics and informal care utilisation were recorded. Current health was evaluated by the EQ-5D generic health status questionnaire and time trade-off (TTO) methods. Happiness was measured on a visual analogue scale (VAS). Subjective life-expectancy and expected EQ-5D status at ages 70, 80 and 90 were surveyed. T-test was applied to compare subgroups and Pearson correlations were performed to analyse relationships between variables. RESULTS: One hundred twenty two patients were involved (females 62%) with a mean (SD) age of 75.2 (7.9) years and disease duration of 2.9 (2.5) years. The majority were in AREDS-4 state, the better eye's ETDRS was 64.7 (15.4). EQ-5D and TTO revealed moderate deterioration of health (0.66 vs. 0.72, p = 0.131), happiness VAS was 6.3 (2.2). Correlation between EQ-5D and ETDRS was moderate (R = 0.242, p < 0.05) and having both versus one eye in AREDS-4 resulted lower TTO (0.68 vs. 0.83; p = 0.013). Subjective life-expectancy did not differ significantly from statistical life-expectancy and had no significant impact on TTO. The self-estimated mean EQ-5D score was 0.60, 0.40 and 0.24 for ages 70, 80 and 90 which is lower than the population norm of age-groups 65-74, 75-84 and 85+ (0.77, 0.63 and 0.63, respectively). Age, gender, current EQ-5D, need for informal care and happiness were deterministic factors of subjective health expectations. CONCLUSION: AMD patients with antiVEGF treatment have comparable HRQOL as the age-matched general public but expect a more severe deterioration of health with age. Older patients with worse HRQOL have worse subjective expectations. Exploring patients' health expectations provides an opportunity for ophthalmologists to correct misperceptions and improve the quality of AMD care. Further studies should provide evidences on the relationship between subjective expectations and actual health outcomes, and on its impact on patients' AMD-specific health behaviour.

[Regional disparities in the prevalence of diabetes and diabetic retinopathy in Hungary in people aged 50 years and older]. / Cukorbetegség és retinopathia diabetica regionális egyenlotlenségei Magyarországon az 50 éves és idosebb korú lakosság körében.

INTRODUCTION: Diabetes mellitus (DM) is one of the main causes of blindness among persons aged 50 years and older. AIM: The purpose of our survey was to estimate the prevalence of DM and diabetic retinopathy (DR), as well as to assess the coverage of diabetic eye care services in different regions of Hungary. METHOD: In 105 clusters, 3675 people aged 50 years and older were included in the survey. The standardized rapid assessment of avoidable blindness (RAAB) with the diabetic retinopathy module (DRM) was used to examine the participants. Thereafter, differences between West-, Middle- and East-Hungary were analysed. RESULTS: Prevalence of DM was higher in East-Hungary (20.9%), than in West- (19.5%) and in Middle-Hungary (19.5%). Prevalence od DR was higher in West-Hungary (24.1%), than in Middle- (17.8%) and in East-Hungary (19.6%). Proportion of participants who never had a fundus examination for DR was the lowest in Middle-Hungary (19.1%). CONCLUSIONS: Primary care should be strenghten mainly in country settlements or telemedical eye screening program should be started to decrease the prevalence of diabetic eye complications. Orv. Hetil., 2017, 158(10), 362-367.

Diabetes and diabetic retinopathy in people aged 50†years and older in Hungary.

BACKGROUND/AIMS: The purpose of this study was to estimate the prevalence of diabetes mellitus (DM) and diabetic retinopathy (DR) in the population aged 50 years and older in Hungary, and to assess the coverage of diabetic eye care services. METHODS: In total, 105 clusters of 35 people aged 50 years or older were randomly selected. The standardised rapid assessment of avoidable blindness (RAAB) with the diabetic retinopathy module (DRM) was used. Participants were classified as having DM if they were known to have DM or if their random blood glucose level was ≥200 mg/dL. Dilated fundus examination and Scottish DR grading were performed. RESULTS: In total, 3523 (95.9%) out of 3675 eligible subjects were examined. And 705 (20.0%) out of 3523 had known (661) or newly diagnosed DM (44). Twenty per cent of participants with known DM had a blood glucose level ≥200 mg/dL, and 27.4% had never had an ophthalmological examination for DR. Prevalence of DR and/or maculopathy was 20.7% and prevalence of sight-threatening DR (STDR) was 4.3% in one or both eyes among participants with DM. CONCLUSIONS: Prevalence of DM was in line with findings of other RAAB+DRM surveys and slightly lower than the unpublished earlier age-matched Hungarian estimate. Prevalence of DR was slightly lower than expected. The prevalence of STDR was low in people aged 50 years and older in Hungary compared with the results of other RAAB with DRM surveys. DR screening coverage was low. To prevent severe complications of DM and possible concomitant visual loss, the coverage of ophthalmic examinations in patients with DM should be increased.

Leber congenital amaurosis: first genotyped Hungarian patients and report of 2 novel mutations in the CRB1 and CEP290 genes.

PURPOSE: To introduce the first Hungarian patients with genetically defined Leber congenital amaurosis (LCA) and to report 2 novel mutations. METHODS: Seven otherwise healthy patients (4-29 years, 5 male and 2 female) who had an onset of severe visual impairment before age 2 years were investigated. The diagnosis was established in all individuals by medical history, funduscopy, and full-field electroretinogram (ERG). Ocular examination included visual acuity testing, digital fundus photography, and in 6 patients retinal imaging with optical coherence tomography (OCT). Arrayed primer extension microarray screening was performed in all probands. In 2 patients, further Sanger sequencing and targeted next-generation sequencing revealed the second disease allele. RESULTS: A cone-rod type LCA was revealed in 4 patients and a rod-cone type disease in 3 patients. Five patients presented with maculopathy. Optical coherence tomography (OCT) imaging showed diffuse retinal thickening in 3 probands with severe macular atrophy in one. Full-field ERGs were undetectable or residual in all patients. Genetic screening revealed AIPL1, CRB1, and CEP290 gene-related pathology in 6 patients; in 1 proband, no mutation was found. Three homozygous and 3 compound heterozygous mutations were identified. Two novel variants were detected: c.2536G>T (p.G846X) in the CRB1 gene and c.4929delA (p.Lys1643fsX2) in the CEP290 gene. CONCLUSIONS: Genetic subtypes identified are among the most common ones in LCA; the phenotypes are consistent with those reported previously. Both novel mutations are predicted to result in a premature translation termination. The phenotype related to the novel CRB1 mutation results in severe atrophic maculopathy.

Characterization of connexin36 gap junctions in the human outer retina.

Retinal connexins (Cx) form gap junctions (GJ) in key circuits that transmit average or synchronize signals. Expression of Cx36, -45, -50 and -57 have been described in many species but there is still a disconcerting paucity of information regarding the Cx makeup of human retinal GJs. We used well-preserved human postmortem samples to characterize Cx36 GJ constituent circuits of the outer plexiform layer (OPL). Based on their location, morphometric characteristics and co-localizations with outer retinal neuronal markers, we distinguished four populations of Cx36 plaques in the human OPL. Three of these were comprised of loosely scattered Cx36 plaques; the distalmost population 1 formed cone-to-rod GJs, population 2 in the mid-OPL formed cone-to-cone GJs, whereas the proximalmost population 4 likely connected bipolar cell dendrites. The fourth population (population 3) of Cx36 plaques conglomerated beneath cone pedicles and connected dendritic tips of bipolar cells that shared a common presynaptic cone. Overall, we show that the human outer retina displays a diverse cohort of Cx36 GJ that follows the general mammalian scheme and display a great functional diversity.

In Vivo Confocal Microscopic Imaging of the Cornea After Femtosecond and Excimer Laser-assisted Penetrating Keratoplasty.

PURPOSE: To examine the microstructure of the cornea after excimer and femtosecond laser-assisted penetrating keratoplasty (ELAK and FLAK) in eyes with Fuchs' dystrophy and keratoconus. METHODS: Fifty-seven patients were divided into four groups according to corneal disease and surgical technique: Fuchs' dystrophy and ELAK (n = 9; mean age: 70.4 ± 10.6 years); Fuchs' dystrophy and FLAK (n = 13; mean age: 64.3 ± 11.2 years); keratoconus and ELAK (n = 9; mean age: 47.4 ± 13.9 years); and keratoconus and FLAK (n = 9; mean age: 43.5 ± 13.8 years). The control group comprised individuals without ocular disease (n = 17; mean age: 39.9 ± 17.3 years). In vivo investigation of the corneal graft and graft-host junction zone was performed with confocal corneal microscopy. RESULTS: All corneal grafts were transparent and no rejection reaction could be observed during the follow-up period. Confocal microscopy revealed no difference in basal epithelial cell density compared to controls. Anterior keratocyte density was lower than in the control group (818 ± 131 cells/mm(2)) in all four treatment groups (596 ± 174, 586 ± 113, 529 ± 75, 552 ± 91 cells/mm(2)). Langerhans cells could barely be seen; there was no difference in the cutting edge configuration and wound integrity. CONCLUSIONS: In vivo confocal microscopy provided evidence that good alignment of graft-host junction could be created with both techniques. The excimer laser was not inferior to the femtosecond laser in performing corneal cuts. The low density of Langerhans cells revealed well-controlled cellular immunological response and sustained corneal integrity in both laser groups.

Isotonic Glycerol and Sodium Hyaluronate Containing Artificial Tear Decreases Conjunctivochalasis after One and Three Months: A Self-Controlled, Unmasked Study.

UNLABELLED: Dry eye complaints are ranked as the most frequent symptoms of patients visiting ophthalmologists. Conjunctivochalasis is a common dry eye disorder, which can cause an unstable tear film and ocular discomfort. The severe conjunctivochalasis characterized by high LId-Parallel COnjunctival Folds (LIPCOF) degree usually requires surgical intervention, where a conservative therapy would be highly desirable. Here we examined the efficacy of a preservative-free, inorganic salt-free unit-dose artificial tear, called Conheal containing isotonic glycerol and 0.015% sodium hyaluronate in a prospective, unmasked, self-controlled study involving 20 patients. The regular use of the glycerol/hyaluronate artificial tear in three months caused a significant improvement in the recorded parameters. Conjunctivochalasis decreased from a mean LIPCOF degree of 2.9 ± 0.4 on both eyes to 1.4 ± 0.6 on the right (median decrease of -2 points, 95% CI from -2.0 to -1.0), and to 1.4 ± 0.7 on the left eye (median decrease of -1 points, 95% CI from -2.0 to -1.0) (p<0.001 for both sides). The tear film breakup time (TFBUT) lengthened from 4.8 ± 1.9 seconds on both eyes to 5.9 ± 2.3 seconds (mean increase of 1.1 seconds, 95% CI from 0.2 to 2.0) and 5.7 ± 1.8 seconds (mean increase of 0.9 seconds, 95% CI from 0.3 to 1.5) on the right and left eyes, respectively (p(right eyes) = 0.020, p(left eyes) = 0.004). The corneal lissamine staining (Oxford Scheme grade) was reduced from 1.3 ± 0.6 on the right and 1.4 ± 0.6 on the left eye significantly (p<0.001) to 0.3 ± 0.4 and 0.2 ± 0.4 on the right and the left eyes. The Ocular Surface Disease Index (OSDI) questionnaire score indicating the subjective complaints of the patients also decreased from a mean value of 36.2 ± 25.3 to 15.6 ± 16.7 (p<0.001). In this study, the artificial tear, Conheal decreased the grade of the conjunctivochalasis significantly after one month of regular use already, from the LIPCOF degree 3, considered as indication of conjunctival surgery, to a LIPCOF degree 2 or lower requiring a conservative therapy. Our results raise the possibility that vision-related quality of life can be significantly improved by conservative therapies even in severe conjunctivochalasis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN81112701 http://www.isrctn.com/ISRCTN81112701.