Indications and Outcomes of Intraocular Lens Explantation in a Tertiary Eyecare Center in Hungary between 2006 and 2020.

Purpose: Our study aimed to evaluate the indications and outcomes of intraocular lens (IOL) explantation surgeries in a tertiary eyecare center in Hungary. Materials and Methods: This retrospective study included all IOL explantation surgeries performed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University, Budapest, Hungary. There were no exclusion criteria for this study. For each patient, the demographics, clinical history, preoperative status, indications for IOL explantation, and operative and postoperative details were reviewed. Primary outcomes included explantation indications and the type of secondary implanted IOL. Results: A total of 161 eyes from 153 patients were included (96 males; 62.7%); age at the time of the IOL explantation was 65.0 ± 17.4 years. The mean time between primary cataract surgery and IOL explantation was 8.5 ± 7.7 years. In total, 139 (86.3%) PCIOLs and 22 (13.7%) ACIOLs were explanted. The main indications for IOL explantation were dislocation (n = 133; 95.7%) and refractive cause (n = 2; 1.4%) in the PCIOL group. Among ACIOL explantations, the main reasons were pseudophakic bullous keratopathy (n = 14; 63.6%), dislocation (n = 4; 18.2%), and refractive cause (n = 2; 9.1%). In the PCIOL group, 115 (82.7%) primary IOLs were implanted in the capsular bag, 16 (11.5%) were sulcus fixated, and 8 (5.8%) were scleral fixated. The most frequent ocular comorbidities were previous vitrectomy (n = 50, 31.1%), previous ocular trauma (n = 45, 28.0%), glaucoma (n = 16, 9.9%), pseudoexfoliation syndrome (n = 15, 9.3%), and high axial myopia (n = 14, 8.7%). The most commonly used secondary IOL implant was the prepupillary iris-claw IOL (n = 115, 73.7%), followed by the retropupillary iris-claw IOL (n = 32, 20.5%). Uncorrected visual acuity (UCVA) was significantly better following IOL exchange in the entire sample (1.57 ± 0.61 (range: 2.40-0.05) vs. 0.77 ± 0.56 (range: 2.40-0.00); p < 0.001). Best-corrected visual acuity (BCVA) was maintained or improved in 80.7% of cases after IOL explantation. Conclusions: The most common indication for IOL explantation at a tertiary eyecare center in Hungary is IOL dislocation, followed by pseudophakic bullous keratopathy. Prepupillary and retropupillary iris-claw IOL are the most frequently used secondary implants and their use resulted in a significant UCVA improvement following IOL exchange.

EZH2 Expression in Head-and-Neck Squamous Cell Cancer in Young Patients.

EZH2 (Enhancer of zeste homolog 2) promotes tumor growth and survival through numerous mechanisms and is a promising target for novel therapeutic approaches. We aimed to characterize the expression of EZH2 in the tumors of young head-and-neck squamous cell cancer (HNSCC) patients in comparison with the general HNSCC patient population. We used formalin-fixed, paraffin-embedded tissue blocks from 68 random young HNSCC patients (≤39 years, median age: 36 years; diagnosed between 2000 and 2018), which were compared with the samples of 58 age- and gender-matched general HNSCC subjects (median age: 62 years; all diagnosed in the year 2014). EZH2 and p53 expression of the tumors was detected using immunohistochemical staining. Lower EZH2 expression was found to be characteristic of the tumors of young HNSCC patients as opposed to the general population (median EZH2 staining intensity: 1 vs. 1.5 respectively, p < 0.001; median fraction of EZH2 positive tumor cells: 40% vs. 60%, respectively, p = 0.003, Mann-Whitney). Cox analysis identified a more advanced T status (T3-4 vs. T1-2), a positive nodal status, and alcohol consumption, but neither intratumoral EZH2 nor p53 were identified as predictors of mortality in the young patient group. The lower EZH2 expression of young HNSCC patients' tumors discourages speculations of a more malignant phenotype of early-onset tumors and suggests the dominant role of patient characteristics. Furthermore, our results might indicate the possibility of an altered efficacy of the novel anti-EZH2 therapies in this patient subgroup.

International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

BACKGROUND: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration. METHODS: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations. RESULTS: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail. CONCLUSIONS: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection.

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.

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.

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.

Dosimetric comparison of postoperative interstitial high-dose-rate brachytherapy and modern external beam radiotherapy modalities in tongue and floor of the mouth tumours in terms of doses to critical organs.

BACKGROUND: The aim of the study was to dosimetrically compare interstitial high-dose-rate (HDR) brachytherapy (BT) and modern external beam radiotherapy modalities, as volumetric modulated arc therapy (VMAT) and stereotactic radiotherapy with Cyberknife (CK) of tumours of the tongue and floor of the mouth in terms of dose to the critical organs. PATIENTS AND METHODS: In National Institute of Oncology, Budapest, between March 2013 and August 2022 twenty patients (11 male/9 female) with stage T1-3N0M0 tongue (n = 14) and floor of mouth (n = 6) tumours received postoperative radiotherapy because of close/positive surgical margin and/or lymphovascular and/or perineural invasion. High-dose-rate interstitial brachytherapy applying flexible plastic catheters with a total dose of 15 × 3 Gy was used for treatment. In addition to BT plans VMAT and stereotactic CK plans were also made in all cases, using the same fractionation scheme and dose prescription. As for the organs at risk, the doses to the mandible, the ipsilateral and the contralateral salivary glands were compared. RESULTS: The mean volume of the planning target volume (PTV) was 12.5 cm3, 26.5 cm3 and 17.5 cm3 in BT, VMAT and CK techniques, respectively, due to different safety margin protocols. The dose to the mandible was the most favourable with BT, as for the salivary glands (parotid and submandibular) the CK technique resulted in the lowest dose. The highest dose to the critical organs was observed with the VMAT technique. The mean values of D2cm3 and D0.1cm3 for the critical organs were as follows for BT, VMAT and CK plans: 47.4% and 73.9%, 92.2% and 101.8%, 68.4% and 92.3% for the mandible, 4.8% and 6.7%, 7.3% and 13.8%, 2.3% and 5.1% for the ipsilateral parotid gland, 3.5% and 4.9%, 6.8% and 10.9%, 1.5% and 3.3% for the contralateral parotid gland, 7.3% and 9.4%, 9.0% and 14.3%, 3.6% and 5.6% for the contralateral submandibular gland. CONCLUSIONS: The present results confirm that BT, despite being an invasive technique, is dosimetrically clearly beneficial in the treatment of oral cavity tumours and is a modality worth considering when applying radiotherapy, not only as definitive treatment, but also postoperatively. The use of the CK in the head and neck region requires further investigation.

Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

Most of the neck node metastases from cancer of unknown primary (CUP) are squamous cell carcinomas (SCCs). The majority of which are human papillomavirus (HPV)-related, frequently show cystic morphology referring to Waldeyer's ring origin. Here, we report four cases of neck node SCCs metastases from CUP. In our institute, 432 patients with head and neck (HN) SCC underwent pretreatment mutagen sensitivity (MS) assay between 1996 and 2006. Among them, 4 patients ≤50 years of age had metastatic cervical nodes from CUP. The primary treatment was cervical node dissection ± radiotherapy. All patients had elevated (>1.0 chromatid break/cell) MS. One male patient died of progressive neck metastasis within 3 years and the 3 female patients are still alive more than 15 years after initial treatment of HPV+ (two) or cystic (one) SCC. Two female patients developed second and third distant site metachronous primary cancers. HPV+ or cystic HNSCC from CUP with elevated MS indicates good outcome. Distant site metachronous cancers of different histologic origins cannot be explained by field cancerization. The clinical significance of elevated MS in neck node SCC metastasis from CUP requires further investigation.

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.

First-in-Human Safety Study of Femtosecond Laser Image-Guided Trabeculotomy for Glaucoma Treatment: 24-month Outcomes.

Purpose: Pilot study to evaluate adverse events and intraocular pressure (IOP)-lowering of a novel, noninvasive glaucoma procedure, femtosecond laser, image-guided, high-precision trabeculotomy (FLIGHT). Design: Prospective, nonrandomized, single-center, interventional, single-arm clinical trial. Participants: Eighteen eyes from 12 patients with open-angle glaucoma. Methods: Eighteen eyes from 12 patients underwent FLIGHT, creating a single channel measuring 500-µm wide by 200-µm high through the trabecular meshwork and into Schlemm's canal. Adverse events, IOP, and other parameters were evaluated out to 24 months. Main Outcome Measures: Outcomes were the rates and types of adverse events and the rate of postprocedure best-corrected visual acuity loss (≥ 2 lines) compared with baseline. Efficacy outcomes were reduction in mean intraocular pressure (IOP) with respect to baseline and the percentage of eyes with a ≥ 20% reduction in IOP. Results: Eighteen eyes from 12 patients were enrolled in the study; 11 patients (17 eyes) returned at 24 months. There were no serious adverse events related to the laser treatment. Well-defined channels were clearly visible at 24 months by gonioscopy and anterior segment OCT, with no evidence of closure. At 24 months, the mean IOP was reduced by 34.6% from 22.3 ± 5.5 to 14.5 ± 2.6 mmHg (P < 5e-5), with an average of 2.0 ± 1.2 hypotensive medications compared with 2.2 ± 1.1 at baseline (P = 0.22). Fourteen out of the 17 study eyes (82.3%) achieved a ≥ 20% reduction in IOP at 24 months when compared with baseline. Conclusion: The FLIGHT system demonstrated a favorable safety profile in this initial pilot study, with no device-related serious adverse events. The channels appeared patent at 24 months, indicating medium-term durability. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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.

The characteristics of head and neck squamous cell cancer in young adults: A retrospective single-center study.

We aimed to characterize clinical and prognostical factors of primary head and neck squamous cell carcinoma (HNSCC) in 85 young patients (≤39 years, median age: 37 years; between 2000-2018) in comparison with 140 institutional general HNSCC patients (median age: 61.5 years). The patient's medical records were collected from the institutional database. The prevalence of smoking and alcohol consumption (65.8% and 48.1%) in the young group exceeded the regional population average but was below the institutional (86.4% and 55%) general HNSCC patient population. Primary tumor sites in the group of young patients were as follows: oral cavity (56.4%), oropharynx (17.6%), hypopharynx (11.7%), and larynx (14.1%). Cumulative five-year overall survival was 44.2% in the young group, but significantly better with early T (T1-2 vs. T3-4: 52.6% vs. 26.7%; p = 0.0058) and N0 status (N0 vs. N+: 65.2% vs. 32.3%; p = 0.0013). Young age, abstinence, earlier stage and laryngeal tumor site might predict a better prognosis. The age distribution and the high prevalence of traditional risk factors among the young patients as well as the predominance of oral cavity tumor localization suggest that the early onset of tumor development could be originated from the premature failure of the intrinsic protective mechanisms.

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.

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.

Are active dwell positions always necessary in the ring/ovoids channel of the cervical applicator in the intracavitary-interstitial brachytherapy of cervical cancer?

Purpose: To compare dosimetric parameters of brachytherapy (BT) treatment plans made with or without active source positions of the ring/ovoid (R/O) applicator in locally advanced cervical cancer patients. Material and methods: Sixty patients with cervical cancer without vaginal involvement were selected for the study, who received intra-cavitary/interstitial BT. For each patient, two plans with and without active source dwell positions in R/O were created, using the same dose-volume constraints. EQD2 total doses from external beam and BT of target volumes and organs at risk (OARs) between the competing plans were compared. Results: There was no significant difference in the dose of high-risk clinical target volume (HR-CTV) and gross tumor volume (GTV) between the plans with inactive vs. active R/O. The mean D98 of intermediate-risk clinical target volume (IR-CTV) was significantly lower with inactive R/O; however, the GEC-ESTRO (EMBRACE II study) and ABS criteria were fulfilled in 96% in both plans. There was no difference in dose homogeneity, but conformity of the plans with inactive R/O was higher. Doses to all OARs were significantly lower in plans without R/O activation. While all the plans without R/O activation fulfilled the recommended dose criteria for OARs, it was less achievable with R/O activation. Conclusions: Inactivation of R/O applicator results in similar dose coverage of the target volumes with lower doses to all OARs, as activation of R/O in cervix cancer patients when HR-CTV does not extend to R/O applicator. The use of active source positions in R/O shows worse performance regarding the fulfilment of the recommended criteria for OARs.

[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.

Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration.

PURPOSE: To detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept. PATIENTS AND METHODS: Twenty-one patients (age: 77.85 ± 9.21 years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75 ± 12.67 years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50 µl) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system. RESULTS: A significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37 ± 6.65 vs. 9.44 ± 6.55 µg/ml; p = 0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05 ± 0.01 µg/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04 µg/ml; p = 0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r = 0.02; p = 0.95). CONCLUSION: According to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.

Reaction kinetics determination and uncertainty analysis for the synthesis of the cancer drug lomustine.

Fast and reliable model development frameworks are required to support current trends in modernization of pharmaceutical processing, promoting the use of digital platforms to assist process design and operation. In this work, we use a parameter estimation framework built into the PharmaPy library to determine rate parameters and uncertainty regions of different mechanistic and semi-empirical kinetic expressions for the synthesis of the drug lomustine. The parameter estimation procedure was complemented by identifiability analysis, resulting in simplified reaction mechanisms. Comparison of parameters and their uncertainty in process design was demonstrated through design space analysis, showing important differences in model prediction and the extent of their corresponding design spaces. The results of this work can serve to analyze lomustine manufacturing processes that include separation and isolation steps, where parametric sensitivity is expected to propagate along the manufacturing line and impact process feasible operation, and attainment of critical quality attributes of the product.

Continuous Extraction of 2-Chloroethyl isocyanate for 1-(2-chloroethyl)-3-cyclohexylurea Purification.

This study details the development of simulation-aided design, development, and successful operation of a continuous liquid-liquid extraction platform made with 1.5 mm tubing for the extraction of 2-chloroethyl isocyanate, an important reagent in the synthesis of cancer drugs. Preliminary solvent screening was carried out with partition coefficient calculations to determine solvents of interest. Next, batch and flow extraction experiments of 2-chloroethyl isocyanate in 2-methyl tetrahydrofuran and water were conducted to estimate extraction parameters. Following parameter estimation, experimental and model values for KLa were determined in the range of 1.13×10-3 to 36.0×10-3 s-1. Simulations of the extraction of 2-chloroethyl isocyanate were found to agree with experimental data resulting in a maximum efficiency of 77% and percent extraction of 69% for the continuous platform. Finally, model selection and discrimination was implemented for design space generation with experimental and model determined KLa values to guide lab-scale operation.